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  • 1. Abbas, Sascha
    et al.
    Linseisen, Jakob
    Rohrmann, Sabine
    Chang-Claude, Jenny
    Peeters, Petra H
    Engel, Pierre
    Brustad, Magritt
    Lund, Eiliv
    Skeie, Guri
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Kaaks, Rudolf
    Boeing, Heiner
    Buijsse, Brian
    Adarakis, George
    Ouranos, Vassilis
    Trichopoulou, Antonia
    Masala, Giovanna
    Krogh, Vittorio
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    Buckland, Genevieve
    Suárez, Marcial Vicente Argüelles
    Sánchez, Maria-José
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Amiano, Pilar
    Manjer, Jonas
    Wirfält, Elisabet
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Bueno-de-Mesquita, H B
    van Duijnhoven, Fränzel J B
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J
    Fedirko, Veronika
    Romieu, Isabelle
    Gallo, Valentina
    Norat, Teresa
    Wark, Petra A
    Riboli, Elio
    Dietary intake of vitamin D and calcium and breast cancer risk in the European prospective investigation into cancer and nutrition2013In: Nutrition and Cancer, ISSN 0163-5581, E-ISSN 1532-7914, Vol. 65, no 2, p. 178-187Article in journal (Refereed)
    Abstract [en]

    Studies assessing the effects of vitamin D or calcium intake on breast cancer risk have been inconclusive. Furthermore, few studies have evaluated them jointly. This study is the largest so far examining the association of dietary vitamin D and calcium intake with breast cancer risk in the European Prospective Investigation into Cancer and Nutrition. During a mean follow-up of 8.8 yr, 7760 incident invasive breast cancer cases were identified among 319,985 women. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for pre- and postmenopausal breast cancer risk. Comparing the highest with the lowest quintile of vitamin D intake, HR and 95% CI were 1.07 (0.87-1.32) and 1.02 (0.90-1.16) for pre- and postmenopausal women, respectively. The corresponding HR and 95% CIs for calcium intake were 0.98 (0.80-1.19) and 0.90 (0.79-1.02), respectively. For calcium intake in postmenopausal women, the test for trend was borderline statistically significant (P(trend) = 0.05). There was no significant interaction between vitamin D and calcium intake and cancer risk (P(interaction) = 0.57 and 0.22 in pre- and postmenopausal women, respectively). In this large prospective cohort, we found no evidence for an association between dietary vitamin D or calcium intake and breast cancer risk.

  • 2. Ademuyiwa, Adesoji O.
    et al.
    Arnaud, Alexis P.
    Drake, Thomas M.
    Fitzgerald, J. Edward F.
    Poenaru, Dan
    Bhangu, Aneel
    Harrison, Ewen M.
    Fergusson, Stuart
    Glasbey, James C.
    Khatri, Chetan
    Mohan, Midhun
    Nepogodiev, Dmitri
    Soreide, Kjetil
    Gobin, Neel
    Freitas, Ana Vega
    Hall, Nigel
    Kim, Sung-Hee
    Negeida, Ahmed
    Khairy, Hosni
    Jaffry, Zahra
    Chapman, Stephen J.
    Tabiri, Stephen
    Recinos, Gustavo
    Amandito, Radhian
    Shawki, Marwan
    Hanrahan, Michael
    Pata, Francesco
    Zilinskas, Justas
    Roslani, April Camilla
    Goh, Cheng Chun
    Irwin, Gareth
    Shu, Sebastian
    Luque, Laura
    Shiwani, Hunain
    Altamimi, Afnan
    Alsaggaf, Mohammed Ubaid
    Spence, Richard
    Rayne, Sarah
    Jeyakumar, Jenifa
    Cengiz, Yucel
    Raptis, Dmitri A.
    Fermani, Claudio
    Balmaceda, Ruben
    Marta Modolo, Maria
    Macdermid, Ewan
    Chenn, Roxanne
    Yong, Cheryl Ou
    Edye, Michael
    Jarmin, Martin
    D'amours, Scott K.
    Iyer, Dushyant
    Youssef, Daniel
    Phillips, Nicholas
    Brown, Jason
    Dickfos, Marilla
    Mitul, Ashrarur Rahman
    Mahmud, Khalid
    Oosterkamp, Antje
    Assouto, Pamphile A.
    Lawani, Ismail
    Souaibou, Yacoubou Imorou
    Devadasar, Giridhar H.
    Chong, Chean Leung
    Qadir, Muhammad Rashid Minhas
    Aung, Kyaw Phyo
    Yeo, Lee Shi
    Castillo, Vanessa Dina Palomino
    Munhoz, Monique Moron
    Moreira, Gisele
    Palomino Castillo, Vanessa Dina
    Barros De Castro Segundo, Luiz Carlos
    Khouri Ferreira, Salim Anderson
    Careta, Maira Cassa
    Araujo, Rafael
    Menegussi, Juliana
    Leal, Marisa
    Barroso de Lima, Caio Vinicius
    Tatagiba, Luiza Sarmento
    Leal, Antonio
    Nigo, Samuel
    Kabba, Juana
    Ngwa, Tagang Ebogo
    Brown, James
    King, Sebastian
    Zani, Augusto
    Azzie, Georges
    Firdouse, Mohammed
    Kushwaha, Sameer
    Agarwal, Arnav
    Bailey, Karen
    Cameron, Brian
    Livingston, Michael
    Horobjowsky, Alexandre
    Deckelbaum, Dan L.
    Razek, Tarek
    Montes, Irene
    Sierra, Sebastian
    Mendez, Manuela
    Isabel Villegas, Maria
    Mendoza Arango, Maria Clara
    Mendoza, Ivan
    Aristiza Ibal, Fred Alexander Naranjo
    Montoya Botero, Jaime Andres
    Quintero Riaza, Victor Manuel
    Restrepo, Jakeline
    Morales, Carlos
    Cruz, Herman
    Munera, Alejandro
    Karlo, Robert
    Domini, Edgar
    Mihanovic, Jakov
    Radic, Mihael
    Zamarin, Kresimir
    Pezelj, Nikica
    Khyrallh, Ahmed
    Hassan, Ahamed
    Shimy, Gamal
    Fahmy, Mohamed A. Baky
    Nabawi, Ayman
    Gohar, Muhammad Saad Ali Muhammad
    Elfil, Mohamed
    Ghoneem, Mohamed
    Gohar, Muhammad El-Saied Ahmad Muhammad
    Asal, Mohamed
    Abdelkader, Mostafa
    Gomah, Mahmoud
    Rashwan, Hayssam
    Karkeet, Mohamed
    Gomaa, Ahmed
    Hasan, Amr
    Elgebaly, Ahmed
    Saleh, Omar
    Fattah, Ahmad Abdel
    Gouda, Abdullah
    Elshafay, Abd Elrahman
    Gharib, Abdalla
    Hanafy, Mohammed
    Al-Mallah, Abdullah
    Abdulgawad, Mahmoud
    Baheeg, Mohamad
    Alhendy, Mohammed
    Fattah, Ibrahim Abdel
    Kenibar, Abdalla
    Osman, Omar
    Gemeah, Mostafa
    Mohammed, Ahmed
    Adel, Abdalrahman
    Mesreb, Ahmed Maher Menshawy
    Mohammed, Abdelrahman
    Sayed, Abdelrahman
    Abozaid, Mohamed
    Kotb, Ahmed Hafez El-Badri
    Ata, Ali Amin Ahmed
    Nasr, Mohammed
    Alkammash, Abdelrahman
    Saeed, Mohammed
    El Hamid, Nader Abd
    Attia, Attia Mohamed
    Abd El Galeel, Ahmed
    Elbanby, Eslam
    El-Dien, Khalid Salah
    Hantour, Usama
    Alahmady, Omar
    Mansour, Billal
    Elkorashy, Amr Muhammad
    Taha, Emad Mohamed Saeed
    Lasheen, Kholod Tarek
    Elkolaly, Salma Said
    Abdel-Wahab, Nehal Yosri Elsayed
    Abozyed, Mahmoud Ahmed Fathi
    Adel, Ahmed
    Saeed, Ahmed Moustafa
    El Sayed, Gehad Samir
    Youssif, Jehad Hassan
    Ahmed, Soliman Magdy
    El-Shahat, Nermeen Soubhy
    Khedr, Abd El-Rahman Hegazy
    Elsebaaye, Abdelrhman Osama
    Elzayat, Mohamed
    Abdelraheim, Mohamed
    Elzayat, Ibrahim
    Warda, Mahmoud
    El Deen, Khaled Naser
    Essam, Abdelrhman
    Salah, Omar
    Abbas, Mohamed
    Rashad, Mona
    Elzayyat, Ibrahim
    Hemeda, Dalia
    Tawfik, Gehad
    Salama, Mai
    Khaled, Hazem
    Seisa, Mohamed
    Elshaer, Kareem
    Hussein, Abdelfatah
    Elkhadrawi, Mahmoud
    Afifi, Ahmed Mohamed
    Ebrahim, Osama Saadeldeen
    Metwally, Mahmoud Mohamed
    Elmelegy, Rowida
    Elsawahly, Diaa Moustafa Elbendary
    Safa, Hisham
    Nofal, Eman
    Elbermawy, Mohamed
    Raya, Metwally Abo
    Ghazy, Ahmed Abdelmotaleb
    Samih, Hisham
    Abdelgelil, Asmaa
    Abdelghany, Sarah
    El Kholy, Ahmed
    Elkady, Fatma
    Salma, Mahmoud
    Samy, Sarah
    Fakher, Reem
    Aboarab, Aya
    Samir, Ahmed
    Sakr, Ahmed
    Haroun, Abdelrahman
    Al-Aarag, Asmaa Abdel-Rahman
    Elkholy, Ahmed
    Elshanwany, Sally
    Ghanem, Esraa
    Tammam, Ahmed
    Hammad, Ali Mohamed
    El Shoura, Yousra
    El Ashal, Gehad
    Antar, Sarah
    Mehrez, Sara
    Abdelshafy, Mahmoud
    Hamad, Maha Gamal Mohamad
    Hosh, Mona
    Abdallah, Emad
    Magdy, Basma
    Alzayat, Thuraya
    Gamaly, Elsayed
    Elfeki, Hossam
    Abouzahra, Amany
    Elsheikh, Shereen
    Elgendy, Fatimah I.
    Abd El-Salam, Fathia
    Seifelnasr, Osama
    Ammar, Mohamed
    Eysa, Athar
    Sadek, Aliaa
    Toeema, Aliaa Gamal
    Nasr, Aly
    Abuseif, Mohamed
    Zidan, Hagar
    Barakat, Sara Abd Elmageed
    Elsayed, Nadin
    Abd Elrasoul, Yasmin
    El-Kelany, Ahmed
    Ammar, Mohamed Sabry
    Mustafa, Mennat-Allah
    Makhlouf, Yasmin
    Etman, Mohamed
    Saad, Samar
    Alrahawy, Mahmoud
    Raslan, Ahmed
    Morsi, Mahmoud
    Sabry, Ahmed
    Elwakil, Hager
    Shaker, Heba
    Elkelany, Ahmed
    El-Kashef, Hussein
    Shaalan, Mohamed
    Tarek, Areej
    Elwan, Ayman
    Nayel, Ahmed Ragab
    Seif, Mostafa
    Shafik, Doaa Emadeldin
    Ghoname, Mohamed Ali
    Almallah, Ahmad
    Fouad, Ahmed
    Sayma, Eman Adel
    Elbatahgy, Ahmad
    El-Ma'doul, Angham Solaiman
    Mosad, Ahmed
    Tolba, Hager
    Elsorogy, Diaa Eldin Abdelazeem Amin
    Mostafa, Hassan Ali
    Omar, Amira Atef
    Abd El Hameed, Ola Sherief
    Lasheen, Ahmed
    Abd El Salam, Yasser
    Morsi, Ashraf
    Ismail, Mohammed
    Ahmed, Hager
    Amer, Mohamed A.
    El-Hamouly, Ahmed Sabry
    Attallah, Noura
    Mosalum, Omnia
    Afandy, Ahmed
    Mokhtar, Ahmed
    Abouelnasr, Alaa
    Ayad, Sara
    Shaker, Ramdan
    Sakr, Rokia
    Amreia, Mahmoud
    Elsobky, Soaad
    Mustafa, Mohamed
    El Magd, Ahmed Abo
    Marey, Abeer
    Tarek, Amr
    Fadel, Mohamed
    Mohamed, Mohamed Moamen
    Fadel, Amr
    Ahmed, Emad Ali
    Ali, Ahmad
    Alwafai, Mohammad Ghassan
    Alnawam, Ehab Abdulkader Hemida Ghazy
    Dwydar, Abdullah
    Kharsa, Sara
    Mamdouh, Ehab
    El-Sheemy, Hatem
    Alyoussef, Ibrahim
    Aly, Abouelatta Khairy
    Aldalaq, Ahmad
    Alnawam, Ehab
    Alkhabbaz, Dalia
    Saad, Mahmoud
    Hussein, Shady
    Elazayem, Ahmed Abo
    Meshref, Ahmed
    Elashmawy, Marwa
    Mousa, Mohammed
    Nashaat, Ahmad
    Ghanem, Sara
    Elsayed, Zaynab M.
    Elwaey, Aya
    Elkadsh, Iman
    Darweesh, Mariam
    Mohameden, Ahmed
    Hafez, Mennaallah
    Badr, Ahmed
    Badwy, Assmaa
    Abd El Slam, Mohamed
    Elazoul, Mohamed
    Al-Nahrawi, Safwat
    Eldamaty, Lotfy
    Nada, Fathee
    Ameen, Mohamed
    Hagar, Aya
    Elsehimy, Mohamed
    Abo-ryia, Mohammad
    Dawoud, Hossam
    El Mesery, Shorouk
    El Gendy, Abeer
    Abdelkareem, Ahmed
    Marey, Ahmed Safwan
    Allam, Mostafa
    Shehata, Sherif
    Abozeid, Khaled
    Elshobary, Marwa
    Fahiem, Ahmed
    Sarsik, Sameh
    Hashish, Amel
    Zidan, Mohamed
    Hashish, Mohamed
    Aql, Shaimaa
    Elhendawy, Abdelaziz Osman Abdelaziz
    Husseini, Mohamed
    Khater, Omar
    Kasem, Esraa Abdalmageed
    Gheith, Ahmed
    Elfouly, Yasmin
    Soliman, Ahmed Ragab
    Hani, Yasmein
    Elfouly, Nesma
    Fawzy, Ahmed
    Hassan, Ahmed
    Rashid, Mohammad
    Elsherbiny, Abdallah Salah
    Sieda, Basem
    Badwi, Nermin Mohamed
    Mohammed, Mohammed Mustafa Hassan
    Mohamed, Osama
    Habeeb, Mohammad Abdulkhalek
    Worku, Mengistu
    Starr, Nichole
    Desta, Semay
    Wondimu, Sahlu
    Abebe, Nebyou Seyoum
    Thomas, Efeson
    Asele, Frehun Ayele
    Dabessa, Daniel
    Abebe, Nebiyou Seyoum
    Zerihun, Abebe Bekele
    Scalabre, Aurelien
    Frade, Fernanda
    Irtan, Sabine
    Parent, Valentine
    Martin, Amandine
    Graffeille, Vivien
    Gaignard, Elodie
    Alimi, Quentin
    Abbo, Olivier
    Mouttalib, Sofia
    Bouali, Ourdia
    Hervieux, Erik
    Aigrain, Yves
    Botto, Nathalie
    Faure, Alice
    Fievet, Lucile
    Panait, Nicoleta
    Eyssartier, Emilie
    Schmitt, Francoise
    Podevin, Guillaume
    Muller, Cecile
    Bonnard, Arnaud
    Peycelon, Matthieu
    Abantanga, Francis
    Boakye-Yiadom, Kwaku
    Bukari, Mohammed
    Owusu, Frank
    Awuku-Asabre, Joseph
    Bray, Lemuel Davies
    Lytras, Dimitrios
    Psarianos, Kyriakos
    Bamicha, Anastasia
    Anthoulakis, Christos
    Nikoloudis, Nikolaos
    Mitroudis, Nikolaos
    Estupinian, Sergio
    Forno, Walter
    Guevara, Romeo
    Aguilera, Maria
    Mendez, Napoleon
    Mendizabal, Cesar Augusto Azmitia
    Ramazzini, Pablo
    Urquizu, Mario Contreras
    Rodriguez, Daniel Estuardo Marroquin
    Velsquez, Carlos Ivan Perez
    Merida, Sara Maria Contreras
    Regalado, Francisco
    Lopez, Mario
    Siguantay, Miguel
    Prasad, S. S.
    Kirishnan, Anand
    Gyanchandani, Nidhi
    Bhat, Sriram
    Sreedharan, Anjana
    Kinnera, S. V.
    Nadkami, Shravan
    Lakshmi, Harish Neelamraju
    Malik, Puneet
    Bin Mahamood, Abid
    Khajanchi, Monty
    Satoskar, Savni
    Satoskar, Rajeev
    Reddy, Yella
    Venugopal, Caranj
    Kumar, Sunil
    Sutanto, Eldaa Prisca Refianti
    Soeselo, Daniel Ardian
    Tedjaatmadja, Chintya
    Rahmawati, Fitriana Nur
    Mayasari, Maria
    Al-Hasani, Ruqaya Kadhim Mohammed Jawad
    Al-Hameedi, Hasan Ismael Ibraheem
    Al-Azraqi, Israa Abdullah Aziz
    Sabeeh, Lubna
    Kamil, Rahma
    Rasendran, Amoudtha
    Sheehan, Jacqueline
    Kerley, Robert
    Normile, Caoimhe
    Gilbert, Richard William
    Song, Jiheon
    Mauro, Linnea
    Dablouk, Mohammed Osman
    Kielty, Paul
    Marks, Eleanor
    Gosling, Simon
    Mccarthy, Michelle
    Mirghani, Diya
    Naqvi, Syed Altaf
    Wong, Chee Siong
    Gosling, Simon George
    Fahy, Ciara
    Cadogan, Diana Duarte
    Powell, Anna
    Gilbert, Richard
    Clifford, Caroline
    Driscoll, Aoife
    Paul, Stassen
    Lee, Chris
    Bowe, Ross
    Hutch, William
    Mohan, Helen
    O'Neill, Maeve
    Mealy, Kenneth
    Danelli, Piergiorgio
    Bondurri, Andrea
    Maffioli, Anna
    Bonavina, Luigi
    Macchitella, Yuri
    Ceriani, Chiara
    Veronese, Ezio
    Bortolasi, Luca
    Hasheminia, Alireza
    Benevento, Angelo
    Tessera, Gaetano
    Turati, Luca
    Sgroi, Giovanni
    Rausa, Emanuele
    Venskutonis, Donatas
    Bradulskis, Saulius
    Urbanavicius, Linas
    Austraite, Aiste
    Riauka, Romualdas
    Dambrauskas, Zilvinas
    Coomber, Ross
    Johnson, Kenneth
    Nowers, Jennifer
    Periasammy, Dineshwary
    Salleh, Afizah
    Das, Andre
    Tze, Reuben Goh Em
    Kumar, Milaksh Nirumal
    Abdullah, Nik Azim Nik
    Chong, Hoong Yin
    Agius, Marija
    Borg, Elaine
    Bezzina, Maureen
    Bugeja, Roberta
    Vella-Baldacchino, Martinique
    Spina, Andrew
    Psaila, Josephine
    Francois-Coridon, Helene
    Tolg, Cecilia
    Colombani, Jean-Francois
    Jacobe, Mario
    Mapasse, Domingos
    Snyder, Elizabeth
    Oumer, Ramadan
    Osman, Mohammed
    Mohammad, Aminu
    Anyanwu, Lofty-John
    Sheshe, Abdulrahman
    Adesina, Alaba
    Faturoti, Olubukola
    Taiwo, Ogechukwu
    Ibrahim, Muhammad Habib
    Nasir, Abdulrasheed A.
    Suleiman, Siyaka Itopa
    Adeniyi, Adewale
    Adesanya, Opeoluwa
    Adebanjo, Ademola
    Osuoji, Roland
    Atobatele, Kazeem
    Ogunyemi, Ayokunle
    Wiiliams, Omolara
    Oludara, Mobolaji
    Oshodi, Olabode
    Razzaq, Abdul
    Lawal, Oluwagbemiga
    Alakaloko, Felix
    Elebute, Olumide
    Osinowo, Adedapo
    Bode, Christopher
    Adesuyi, Abidemi
    Tade, Adesoji
    Adekoya, Adeleke
    Nwokoro, Collins
    Ayandipo, Omobolaji O.
    Lawal, Taiwo Akeem
    Ajao, Akinlabi E.
    Ali, Samuel Sani
    Odeyemi, Babatunde
    Olori, Samson
    Popoola, Ademola
    Adeyeye, Ademola
    Adeniran, James
    Lossius, William J.
    Havemann, Ingemar
    Thorsen, Kenneth
    Narvestad, Jon Kristian
    Wold, Trude Beate
    Nymo, Linn
    Elsiddig, Mohammed
    Dar, Manzoor
    Bhopal, Kamran Faisal
    Iftikhar, Zainab
    Furqan, Muhammad Mohsin
    Nighat, Bakhtiar
    Jawaid, Masood
    Khalique, Abdul
    Zil-E-Ali, Ahsan
    Rashid, Anam
    Aguilar, Wendy Leslie Messa
    Chiong, Jose Antonio Cabala
    Cecilia, Ana
    Bautista, Manchego
    Huaman, Eduardo
    Zegarra, Sergio
    Camacho, Rony
    Vergara Celis, Jose Maria
    Romani Pozo, Diego Alonso
    Hamasaki, Jose
    Temoche, Edilberto
    Herrera-Matta, Jaime
    Garcia Torres, Carla Pierina
    Alvarez Barreda, Luis Miguel
    Barrionuevo Ojeda, Ronald Renato
    Garaycochea, Octavio
    Mollo, Melanie Castro
    Delgado, Mitchelle Solange De Fa Tima Linares
    Fujii, Francisco
    Manchego Bautista, Ana Cecilia
    Messa Aguilar, Wendy Leslie
    Cabala Chiong, Jose Antonio
    Aranzabal Durand, Susana Yrma
    Arroyo Basto, Carlos Alejandro
    Urbina Rojas, Nelson Manuel
    Shu Yip, Sebastian Bernardo
    Contreras Vergara, Ana Lucia
    Rosas Moran, Andrea Echevarria
    Borda Luque, Giuliano
    Rodriguez Castro, Manuel
    Alvarado Jaramillo, Ramon
    Sila, George Manrique
    Lopez, Crislee Elizabeth
    De Leon, Mardelangel Zapata Ponze
    Machaca, Massiell
    Coasaca Huaraya, Ronald
    Arenas, Andy
    Herrera Puma, Clara Milagros
    Pino, Wilfredo
    Hinojosa, Christian
    Ponze De Leon, Melanie Zapata
    Limache, Susan
    Manrrique Sila, George
    Mercado Rodriguez, Layza-Alejandra
    Sauvat, Frederique
    Vida, Lucian Corneliu
    Muntean, Liviu Iuliu
    Mironescu, Aurel Sandu
    Alomar, Ibrahim N.
    Alnuqaydan, Saleh A.
    Altwigry, Abdulrahman M.
    Othman, Moayad
    Osman, Nohad
    Alqahtani, Enas
    Alzahrani, Mohammed
    Alyami, Rifan
    Aljohani, Emad
    Alhabli, Ibrahim
    Mikwar, Zaher
    Almuallem, Sultan
    Nawawi, Abrar
    Bakhaidar, Mohamad
    Maghrabi, Ashraf A.
    Alsaggaf, Mohammed
    Aljiffry, Murad
    Altaf, Abdulmalik
    Khoja, Ahmad
    Habeebullah, Alaa
    Akeel, Nouf
    Ghandora, Nashat
    Almoflihi, Abdullah
    Huwait, Abdulmalik
    Al-Shammari, Abeer
    Al-Mousa, Mashael
    Alghamdi, Masood
    Adham, Walid
    Albeladi, Bandar
    Alfarsi, Muayad Ahmed
    Mahdi, Atif
    Al Awwad, Saad
    Nouh, Thamer
    Hassanain, Mazen
    Aldhafeeri, Salman
    Sadig, Nawal
    Algohary, Osama
    Aledrisy, Mohannad
    Gudal, Ahmad
    Alrifaie, Ahmad
    AlRowais, Mohammed
    Althwainy, Amani
    Shabkah, Alaa
    Alamoudi, Uthman
    Alrajraji, Mawaddah
    Alghamdi, Basim
    Aljohani, Saud
    Daqeeq, Abdullah
    Al-Faifi, Jubran J.
    Jennings, Vicky
    Ngayu, Nyawira
    Moore, Rachel
    Kong, Victor
    Sampson, Colleen
    Panieri, Eugenio
    Tun, Myint
    Mphatsoe, Albert Mohale
    Carreira, Jo-Anne
    Teasdale, Ella
    Wagener, Mark
    Botes, Stefan
    Du Plessis, Danelo
    Pagnozzi, Janet
    Quezada, Jimy Harold Jara
    Rodicio, Jose Luis
    Minguez, German
    Rodriguez-Uria, Raquel
    Ugalde, Paul
    Lopez-Arevalo, Camilo
    Barneo, Luis
    Gonzales Stuva, Jessica Patricia
    Aguilar-Jimenez, Jose
    Andres Garcia-Marin, Jose
    Ortega-Vazquez, Irene
    Rodriguez, Lorena
    Herrera, Norberto
    Arachchi, Prasad Pitigala
    Jan, Wanigasekara Senanayake Mudiyanselage Kithsiri
    Arachchige, Lalith Asanka Jayasooriya Jayasooriya
    Sivaganesh, Sivasuriya
    Samaraweera, Dulan Irusha
    Thanusan, Vimalakanthan
    Musa, Ahmed Elgaili Khalid
    Balila, Reem Mohammed Hassan
    Mohamed, Mohamed Awad Elkarim Hamad
    Ali, Hussein
    Elabdin, Hagir Zain
    Hassan, Alaa
    Mahdi, Sefeldin
    Ahmed, Hala
    Idris, Sahar Abdoun Ishag
    Elsayed, Makki
    Elsayed, Mohammed
    Mahmoud, Mohamed
    Thorarinsdottir, Hildur
    Utter, Maria
    Sundstrom, Sami Martin
    Wredberg, Cecilia
    Kjellin, Ann
    Nyberg, Johanna
    Frisk, Bjorn
    Ahlqvist, Sandra
    Bjorklund, Ida
    Hjertberg, Maria
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Andersson, Linda
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Gunnarsson, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Royson, Hanna
    Weber, Per
    Schmid, Roger
    Schivo, Debora
    Despotidis, Vasileios
    Breitenstein, Stefan
    Staerkle, Ralph F.
    Schadde, Erik
    Deichsel, Fabian
    Gerosa, Alexandra
    Nocito, Antonio
    Raptis, Dimitri Aristotle
    Mijuskovic, Barbara
    Zuber, Markus
    Eisner, Lukas
    Kruspi, Swantje
    Reinisch, Katharina Beate
    Schoewe, Christin
    Novak, Allan
    Palma, Adrian F.
    Teufelberger, Gerfried
    Balkan, Ali Zeynel Abidin
    Gumar, Mehmet
    Yavuz, Mehmet Ali
    Karabacak, Ufuk
    Lap, Gokhan
    Ozkan, Bahar Busra
    Adams, Ryan
    Morton, Robert
    Henderson, Liam
    Gratton, Ruth
    Clement, Keiran David
    Chang, Kate Yu-Ching
    McNish, David
    McIntosh, Ryan
    Milligan, William
    Skelly, Brendan
    Anderson-Knight, Hannah
    Lawther, Roger
    Onimowo, Jemina
    Shatkar, Veereanna
    Tharmalingam, Shivanee
    Woin, Evelina
    Fautz, Tessa
    Ziff, Oliver
    Dindyal, Shiva
    Arman, Sam
    Talukder, Shagorika
    Gadhvi, Vijay
    Chew, Luen Shaun
    Heath, Jonathan
    Mannu, Gurdeep Singh
    Zachariades, Dimitris-Christos
    Snaith, Ailsa Claire
    Hettiarachchi, Thusitha Sampath
    Nesaratnam, Arjun
    Wheeler, James
    Sykes, Mark
    Behar, Nebil
    Jordan, Harriet
    Arulampalam, Tan
    Shah, Apar
    Brown, Damien
    Blower, Emma
    Sutton, Paul
    Gasteratos, Konstantinos
    Vimalachandran, Dale
    Magee, Cathy
    Mcguigan, Andrew
    Mcaleer, Stephen
    Morgan, Clare
    Braungart, Sarah
    Lafferty, Kirsten
    Labib, Peter
    Tanase, Andrei
    Mangan, Clodagh
    Reza, Lillian
    Woodward, Helen
    Gouldthorpe, Craig
    Turner, Megan
    Wild, Jonathan R. L.
    Malik, Tom Am
    Proctor, Victoria K.
    Hewage, Kalon
    Davies, James
    Dubois, Andre
    Sarwary, Sayed
    Zardab, Ali
    Grant, Alan
    Mcintyre, Robert
    Tewari, Shirish
    Humm, Gemma
    Farinella, Eriberto
    Parthiban, Sunil
    Hall, Nigel J.
    Wright, Naomi J.
    Major, Christina P.
    Xerri, Thelma
    De Bono, Phoebe
    Amin, Jasim
    Farhad, Mustafa
    Camilleri-Brennan, John F.
    Robertson, Andrew G. N.
    Swann, Joanna
    Richards, James
    Jabbar, Aijaz
    Attard, Myranda
    Burns, Hannah
    Macdonald, Euan
    Baldacchino, Matthew
    Skehan, Jennifer
    Camilleri-Brennan, Julian
    Hall, Tom Falconer
    Gimzewska, Madelaine
    Mclachlan, Greta
    Shah, Jamie
    Giles, James
    Hassan, Maleeha
    Beasley, William
    Vlachogiorgos, Apostolos
    Dias, Stephen
    Maharaj, Geta
    McDonald, Rosie
    Cross, Kate
    Rees, Clare M.
    Van Duren, Bernard
    Upchurch, Emma
    Karandikar, Sharad
    Bowley, Doug
    Karim, Ahmed
    Chachulski, Witold
    Richardson, Liam
    Dawnay, Giles
    Thompson, Ben
    Mistry, Ajayesh
    Ghetia, Millika
    Roy, Sudipta
    Al-Obaedi, Ossama
    Das, Kaustuv
    Prabhudesai, Ash
    Cocker, D. M.
    Tan, Jessica Juliana
    Vivekanantham, Sayinthen
    Gillespie, Michael
    Gudlaugsdottir, Katrin
    Pezas, Theodore
    Currow, Chelise
    Kim, Matthew Young-Han
    Salama, Yahya
    Shah, Rohi
    Ibrahem, Ahmad Aboelkassem
    Ebdewi, Hamdi
    Gravante, Gianpiero
    El-Rabaa, Saleem
    Chan, Zoe
    Hassan, Zaffar
    Makinde, Misty
    Hemingway, David
    Dean, Ramzana
    Boddy, Alexander
    Aber, Ahmed
    Patel, Vijay
    Kotecha, Deevia
    Ubhi, Harmony Kaur
    Hosein, Simon-Peter
    Ward, Simon
    Malik, Kamran
    Jennings, Leifa
    Newton, Tom
    Alkhouri, Mirna
    Kang, Min Kyu
    Houlden, Christopher
    Barry, Jonathan
    Wilson, Michael S. J.
    Neo, Yan Ning
    Ibrahim, Ibrahim
    Chan, Emily
    Peck, Fraser S.
    Lim, Pei J.
    North, Alexander S.
    Blundell, Rebecca
    Williamson, Adam
    Fouad, Dina
    Minocha, Ashish
    Mccarthy, Kathryn
    Court, Emma
    Chambers, Alice
    Yee, Jenna
    Tham, Ji Chung
    Beaton, Ceri
    Walsh, Una
    Lockey, Joseph
    Bokhari, Salman
    Howells, Lara
    Griffiths, Megan
    Yallop, Laura
    Singh, Shailinder
    Nasher, Omar
    Jackson, Paul
    Ramzi, Saed
    Zeidan, Shady
    Doughty, Jennifer
    Sinha, Sidhartha
    Davenport, Ross
    Lewis, Jason
    Duffy, Leo
    Mcaleer, Elizabeth
    Williams, Eleanor
    Obute, Rhalumi Daniel
    Glover, Thomas E.
    Clark, David J.
    Boshnaq, Mohamed
    Akhtar, Mansoor
    Capleton, Pascale
    Doughan, Samer
    Rabie, Mohamed
    Mohamed, Ismail
    Samuel, Duncan
    Dickson, Lauren
    Kennedy, Matthew
    Dempster, Eleanor
    Brown, Emma
    Maple, Natalie
    Monaghan, Eimear
    Wolf, Bernhard
    Garland, Alicia
    Lund, Jonathan
    Boereboom, Catherine
    Murphy, Jennifer
    Tierney, Gillian
    Tou, Samson
    Zimmermann, Eleanor Franziska
    Smart, Neil James
    Warwick, Andrea Marie
    Stasinou, Theodora
    Daniels, Ian
    Findlay-Cooper, Kim
    Mitrasinovic, Stefan
    Ray, Swayamjyoti
    Varcada, Massimo
    D'souza, Rovan
    Omara, Sharif
    Boyce, Tamsin
    Whewell, Harriet
    Jones, Elin
    Ma, Jennifer
    Abington, Emily
    Ramcharn, Meera
    Williams, Gethin
    Winstanley, Joseph
    Kennedy, Ewan D.
    Yeung, Emily N. W.
    Fergusson, Stuart J.
    Jones, Catrin
    O'neill, Stephen
    Lim, Shujing Jane
    Liew, Ignatius
    Nair, Hari
    Fairfield, Cameron
    Oh, Julia
    Koh, Samantha
    Wilson, Andrew
    Fairfield, Catherine
    Th'ng, Francesca
    Robertson, Nichola
    Anandkumar, Delran
    Kirupagaran, Ashok
    Jones, Timothy F.
    Torrance, Hew D.
    Fowler, Alexander J.
    Chandrakumar, Charmilie
    Patel, Priyank
    Ashraf, Syed Faaz
    Lakhani, Sonam M.
    Mclean, Aaron Lawson
    Basson, Sonia
    Batt, Jeremy
    Bowman, Catriona
    Stoddart, Michael
    Benons, Natasha
    Barker, Tom
    Summerour, Virginia
    Harper, Edward
    Smith, Caroline
    Hampton, Matthew
    Mckechnie, Doug
    Farah, Ayaan
    Chun, Anita
    Pereira, Bernadette
    Nemeth, Kristof
    Decker, Emily
    Giuliani, Stefano
    Shalaby, Aly
    Szczap, Aleksandra
    Chidambaram, Swathikan
    Chen, Chee Yang
    Kulasabanathan, Kavian
    Chhabra, Srishti
    Kostov, Elisabeth
    Harbord, Philippe
    Barnacle, James
    Palliyil, Madan Mohan
    Zikry, Mina
    Porter, Johnathan
    Raslan, Charef
    Hafiz, Shazia
    Soltani, Niksa
    Baillie, Katie
    Mirza, Ahmad
    Saeed, Haroon
    Galloway, Simon
    Elena, Gia
    Afzal, Mohammad
    Zakir, Mohamed
    Sodde, Peter
    Hand, Charles
    Sriram, Aiesha
    Clark, Tamsyn
    Holton, Patrick
    Livesey, Amy
    Sinha, Yashashwi
    Iqbal, Fahad Mujtaba
    Bharj, Indervir Singh
    Rotundo, Adriana
    Jenvey, Cara
    Slade, Robert
    Golding, David
    Haines, Samuel
    Abdullah, Ali Adel Ne'ma
    Tilston, Thomas W.
    Loughran, Dafydd
    Donoghue, Danielle
    Giacci, Lorenzo
    Sherif, Mohamed Ashur
    Harrison, Peter
    Tang, Alethea
    Elshaer, Mohamed
    Urbonas, Tomas
    Riaz, Amjid
    Chapman, Annie
    Acharya, Parisha
    Shalhoub, Joseph
    Grossart, Cathleen
    McMorran, David
    Mlotshwa, Makhosini
    Hawkins, William
    Loizides, Sofronis
    Thomson, Peter
    Khan, Shahab
    Taylor, Fiona
    Shukla, Jalak
    Howie, Emma Elizabeth
    Macdonald, Linda
    Komolafe, Olusegun
    Mcintyre, Neil
    Cragg, James
    Parker, Jody
    Stewart, Duncan
    Lintin, Luke
    Tracy, Julia
    Farooq, Tahir
    Sion, Melanie
    Weinstein, Michael S.
    Punja, Viren
    Bugaev, Nikolay
    Goodstein, Monica
    Razmdjou, Shadi
    Determinants of morbidity and mortality following emergency abdominal surgery in children in low-income and middle-income countries2016In: BMJ Global Health, ISSN 2059-7908, Vol. 1, no 4, article id e000091Article in journal (Refereed)
    Abstract [en]

    Background: Child health is a key priority on the global health agenda, yet the provision of essential and emergency surgery in children is patchy in resource-poor regions. This study was aimed to determine the mortality risk for emergency abdominal paediatric surgery in low-income countries globally.

    Methods: Multicentre, international, prospective, cohort study. Self-selected surgical units performing emergency abdominal surgery submitted prespecified data for consecutive children aged <16 years during a 2-week period between July and December 2014. The United Nation's Human Development Index (HDI) was used to stratify countries. The main outcome measure was 30-day postoperative mortality, analysed by multilevel logistic regression.

    Results: This study included 1409 patients from 253 centres in 43 countries; 282 children were under 2 years of age. Among them, 265 (18.8%) were from low-HDI, 450 (31.9%) from middle-HDI and 694 (49.3%) from high-HDI countries. The most common operations performed were appendectomy, small bowel resection, pyloromyotomy and correction of intussusception. After adjustment for patient and hospital risk factors, child mortality at 30 days was significantly higher in low-HDI (adjusted OR 7.14 (95% CI 2.52 to 20.23), p<0.001) and middle-HDI (4.42 (1.44 to 13.56), p=0.009) countries compared with high-HDI countries, translating to 40 excess deaths per 1000 procedures performed.

    Conclusions: Adjusted mortality in children following emergency abdominal surgery may be as high as 7 times greater in low-HDI and middle-HDI countries compared with high-HDI countries. Effective provision of emergency essential surgery should be a key priority for global child health agendas.

  • 3. Agudo, Antonio
    et al.
    Bonet, Catalina
    Sala, Núria
    Muñoz, Xavier
    Aranda, Núria
    Fonseca-Nunes, Ana
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie Christine
    Vineis, Paolo
    Panico, Salvatore
    Palli, Domenico
    Tumino, Rosario
    Grioni, Sara
    Quirós, J Ramón
    Molina, Esther
    Navarro, Carmen
    Barricarte, Aurelio
    Chamosa, Saioa
    Allen, Naomi E
    Khaw, Kay-Tee
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Numans, Mattijs E
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Kaaks, Rudof
    Canzian, Federico
    Boeing, Heiner
    Meidtner, Karina
    Johansson, Mattias
    Umeå University, Faculty of Medicine. WHO, IARC, Lyon, France.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Manjer, Jonas
    Overvad, Kim
    Tjonneland, Anne
    Lund, Eiliv
    Weiderpass, Elisabete
    Jenab, Mazda
    Fedirko, Veronika
    Offerhaus, G Johan A
    Riboli, Elio
    González, Carlos A
    Jakszyn, Paula
    Hemochromatosis (HFE) gene mutations and risk of gastric cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) study2013In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 34, no 6, p. 1244-1250Article in journal (Refereed)
    Abstract [en]

    Hereditary hemochromatosis (HH) is a strong risk factor for hepatocellular cancer, and mutations in the HFE gene associated with HH and iron overload may be related to other tumors, but no studies have been reported for gastric cancer (GC). A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC), including 365 incident gastric adenocarcinoma and 1284 controls matched by center, sex, age and date of blood collection. Genotype analysis was performed for two functional polymorphisms (C282Y/rs1800562 and H63D/rs1799945) and seven tagSNPs of the HFE genomic region. Association with all gastric adenocarcinoma, and according to anatomical localization and histological subtype, was assessed by means of the odds ratio (OR) and 95% confidence interval (CI) estimated by unconditional logistic regression adjusted for the matching variables. We observed a significant association for H63D with OR (per rare allele) of 1.32 (CI = 1.03-1.69). In subgroup analyses, the association was stronger for non-cardia anatomical subsite (OR = 1.60, CI = 1.16-2.21) and intestinal histological subtype (OR = 1.82, CI = 1.27-2.62). Among intestinal cases, two tagSNPs (rs1572982 and rs6918586) also showed a significant association that disappeared after adjustment for H63D. No association with tumors located in the cardia or with diffuse subtype was found for any of the nine SNPs analyzed. Our results suggest that H63D variant in HFE gene seems to be associated with GC risk of the non-cardia region and intestinal type, possibly due to its association with iron overload although a role for other mechanisms cannot be entirely ruled out.

  • 4. Aleksandrova, Krasimira
    et al.
    Bamia, Christina
    Drogan, Dagmar
    Lagiou, Pagona
    Trichopoulou, Antonia
    Jenab, Mazda
    Fedirko, Veronika
    Romieu, Isabelle
    Bueno-de-Mesquita, H. Bas
    Pischon, Tobias
    Tsilidis, Kostas
    Overvad, Kim
    Tjønneland, Anne
    Bouton-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Kaaks, Rudolf
    Kuehn, Tilman
    Tsironis, Christos
    Papatesta, Eleni-Maria
    Saitakis, George
    Palli, Domenico
    Panico, Salvatore
    Grioni, Sara
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H.
    Weiderpass, Elisabete
    Lukic, Marko
    Braaten, Tonje
    Ramon Quiros, J.
    Lujan-Barroso, Leila
    Sanchez, Mara-Jose
    Chilarque, Maria-Dolores
    Ardanas, Eva
    Dorronsoro, Miren
    Nilsson, Lena Maria
    Umeå University, Arctic Research Centre at Umeå University.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Wallström, Peter
    Ohlsson, Bodil
    Bradbury, Kathryn E.
    Khaw, Kay-Tee
    Wareham, Nick
    Stepien, Magdalena
    Duarte-Salles, Talita
    Assi, Nada
    Murphy, Neil
    Gunter, Marc J.
    Riboli, Elio
    Boeing, Heiner
    Trichopoulos, Dimitrios
    The association of coffee intake with liver cancer risk is mediated by biomarkers of inflammation and hepatocellular injury: data from the European Prospective Investigation into Cancer and Nutrition2015In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 102, no 6, p. 1498-1508Article in journal (Refereed)
    Abstract [en]

    Background: Higher coffee intake has been purportedly related to a lower risk of liver cancer. However, it remains unclear whether this association may be accounted for by specific biological mechanisms. Objective: We aimed to evaluate the potential mediating roles of inflammatory, metabolic, liver injury, and iron metabolism biomarkers on the association between coffee intake and the primary form of liver cancer-hepatocellular carcinoma (HCC). Design: We conducted a prospective nested case-control study within the European Prospective Investigation into Cancer and Nutrition among 125 incident HCC cases matched to 250 controls using an incidence-density sampling procedure. The association of coffee intake with HCC risk was evaluated by using multivariable-adjusted conditional logistic regression that accounted for smoking, alcohol consumption, hepatitis infection, and other established liver cancer risk factors. The mediating effects of 21 biomarkers were evaluated on the basis of percentage changes and associated 95% CIs in the estimated regression coefficients of models with and without adjustment for biomarkers individually and in combination. Results: The multivariable-adjusted RR of having >= 4 cups (600mL) coffee/d compared with <2 cups (300 mL)/d was 0.25 (95% CI: 0.11, 0.62; P-trend = 0.006). A statistically significant attenuation of the association between coffee intake and HCC risk and thereby suspected mediation was confirmed for the inflammatory biomarker IL-6 and for the biomarkers of hepatocellular injury glutamate dehydrogenase, alanine aminotransferase, aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), and total bilirubin, which-in combination-attenuated the regression coefficients by 72% (95% CI: 7%, 239%). Of the investigated biomarkers, IL-6, AST, and GGT produced the highest change in the regression coefficients: 40%, 56%, and 60%, respectively. Conclusion: These data suggest that the inverse association of coffee intake with HCC risk was partly accounted for by biomarkers of inflammation and hepatocellular injury.

  • 5. Aleksandrova, Krasimira
    et al.
    Boeing, Heiner
    Nöthlings, Ute
    Jenab, Mazda
    Fedirko, Veronika
    Kaaks, Rudolf
    Lukanova-McGregor, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Center, Heidelberg, Germany.
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Boffetta, Paolo
    Trepo, Elisabeth
    Westhpal, Sabine
    Duarte-Salles, Talita
    Stepien, Magdalena
    Overvad, Kim
    Tjønneland, Anne
    Halkjær, Jytte
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Racine, Antoine
    Lagiou, Pagona
    Bamia, Christina
    Benetou, Vassiliki
    Agnoli, Claudia
    Palli, Domenico
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, Bas
    Peeters, Petra H
    Gram, Inger Torhild
    Lund, Eiliv
    Weiderpass, Elisabete
    Quirós, J Ramón
    Agudo, Antonio
    Sánchez, María-José
    Gavrila, Diana
    Barricarte, Aurelio
    Dorronsoro, Miren
    Ohlsson, Bodil
    Lindkvist, Björn
    Johansson, Anders
    Umeå University, Faculty of Medicine, Department of Odontology. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C
    Riboli, Elio
    Pischon, Tobias
    Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer2014In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, no 3, p. 858-871Article in journal (Refereed)
    Abstract [en]

    Obesity and associated metabolic disorders have been implicated in liver carcinogenesis; however there is little data on the role of obesity-related biomarkers on liver cancer risk. We studied prospectively the association of inflammatory and metabolic biomarkers with risks of hepatocellular carcinoma (HCC), intra-hepatic bile duct (IBD) and gallbladder and bilary tract cancers outside of the liver (GBTC) in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Over an average of 7.7 years, 296 participants developed HCC (n=125), GBTC (n=137) or IBD (n=34). Using risk set sampling, controls were selected in a 2:1 ratio and matched for recruitment center, age, sex, fasting status, time of blood collection. Baseline serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), C-peptide, total, high-molecular-weight (HMW) adiponectin, leptin, fetuin-a, and glutamatdehydrogenase (GLDH) were measured and incidence rate ratios (IRRs) and 95% confidence intervals (CI-s) estimated using conditional logistic regression. After adjustment for lifestyle factors, diabetes, hepatitis infection and adiposity measures, higher concentrations of CRP, IL-6, C-peptide and non-HMW adiponectin were associated with higher risk of HCC (IRR per doubling of concentrations = 1.22; 95%CI = 1.02-1.46, P=0.03; 1.90; 95%CI = 1.30-2.77, P=0.001; 2.25; 95%CI = 1.43-3.54, P=0.0005 and 2.09; 95%CI = 1.19-3.67, P=0.01, respectively). CRP was associated also with risk of GBTC (IRR = 1.22; 95%CI = 1.05-1.42, P=0.01). GLDH was associated with risks of HCC (IRR = 1.62; 95%CI = 1.25-2.11, P=0.0003) and IBD (IRR = 10.5; 95%CI = 2.20-50.90, P=0.003). The continuous net reclassification index was 0.63 for CRP, IL-6, C-peptide and non-HMW adiponectin, and 0.46 for GLDH indicating good predictive ability of these biomarkers. Conclusion: Elevated levels of biomarkers of inflammation and hyperinsulinemia are associated with a higher risk of HCC, independent of obesity and established liver cancer risk factors.

  • 6. Araghi, Marzieh
    et al.
    Galanti, Maria Rosaria
    Lundberg, Michael
    Lager, Anton
    Engström, Gunnar
    Alfredsson, Lars
    Knutsson, Anders
    Norberg, Margareta
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Wennberg, Patrik
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Family Medicine.
    Trolle Lagerros, Ylva
    Bellocco, Rino
    Pedersen, Nancy L.
    Östergren, Per-Olof
    Magnusson, Cecilia
    Use of moist oral snuff (snus) and pancreatic cancer: pooled analysis of nine prospective observational studies2017In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 141, no 4, p. 687-693Article in journal (Refereed)
    Abstract [en]

    While smoking is a well-established risk factor for pancreatic cancer, the effect of smokeless tobacco is less well understood. We used pooled individual data from the Swedish Collaboration on Health Effects of Snus Use to assess the association between Swedish snus use and the risk of pancreatic cancer. A total of 424,152 male participants from nine cohort studies were followed up for risk of pancreatic cancer through linkage to health registers. We used shared frailty models with random effects at the study level, to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for confounding factors. During 9,276,054 person-years of observation, 1,447 men developed pancreatic cancer. Compared to never-snus use, current snus use was not associated with risk of pancreatic cancer (HR 0.96, 95% CI 0.83–1.11) after adjustment for smoking. Swedish snus use does not appear to be implicated in the development of pancreatic cancer in men. Tobacco smoke constituents other than nicotine or its metabolites may account for the relationship between smoking and pancreatic cancer.

  • 7. Bakker, Marije F.
    et al.
    Peeters, Petra H. M.
    Klaasen, Veronique M.
    Bueno-de-Mesquita, H. Bas
    Jansen, Eugene H. J. M.
    Ros, Martine M.
    Travier, Noemie
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Rinaldi, Sabina
    Romieu, Isabelle
    Brennan, Paul
    Boutron-Ruault, Marie-Christine
    Perquier, Florence
    Cadeau, Claire
    Boeing, Heiner
    Aleksandrova, Krasimira
    Kaaks, Rudolf
    Kühn, Tilman
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Vineis, Paolo
    Krogh, Vittorio
    Panico, Salvatore
    Masala, Giovanna
    Tumino, Rosario
    Weiderpass, Elisabete
    Skeie, Guri
    Lund, Eiliv
    Ramon Quirós, J.
    Ardanaz, Eva
    Navarro, Carmen
    Amiano, Pilar
    Sánchez, María-José
    Buckland, Genevieve
    Ericson, Ulrika
    Sonestedt, Emily
    Johansson, Matthias
    Umeå University, Faculty of Medicine, Department of Biobank Research. International Agency for Research on Cancer, Lyon, France.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Travis, Ruth C.
    Key, Timothy J.
    Khaw, Kay-Tee
    Wareham, Nick
    Riboli, Elio
    van Gils, Carla H.
    Plasma carotenoids, vitamin C, tocopherols, and retinol and the risk of breast cancer in the European Prospective Investigation into Cancer and Nutrition cohort2016In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 103, no 2, p. 454-464Article in journal (Refereed)
    Abstract [en]

    Background: Carotenoids and vitamin C are thought to be associated with reduced cancer risk because of their antioxidative capacity.

    Objective: This study evaluated the associations of plasma carotenoid, retinol, tocopherol, and vitamin C concentrations and risk of breast cancer.

    Design: In a nested case-control study within the European Prospective Investigation into Cancer and Nutrition cohort, 1502 female incident breast cancer cases were included, with an oversampling of premenopausal (n = 582) and estrogen receptor-negative (ER-) cases (n = 462). Controls (n = 1502) were individually matched to cases by using incidence density sampling. Prediagnostic samples were analyzed for alpha-carotene, beta-carotene, lycopene, lutein, zeaxanthin, beta-cryptoxanthin, retinol, alpha-tocopherol, gamma-tocopherol, and 454 vitamin C. Breast cancer risk was computed according to hormone receptor status and age at diagnosis (proxy for menopausal status) by using conditional logistic regression and was further stratified by smoking status, alcohol consumption, and body mass index (BMI). All statistical tests were 2-sided.

    Results: In quintile 5 compared with quintile 1, alpha-carotene (OR: 0.61; 95% CI: 0.39, 0.98) and beta-carotene (OR: 0.41; 95% CI: 0.26, 0.65) were inversely associated with risk of ER- breast tumors. The other analytes were not statistically associated with ER- breast cancer. For estrogen receptor-positive (ER+) tumors, no statistically significant associations were found. The test for heterogeneity between ER- and ER+ tumors was statistically significant only for beta-carotene (P-heterogeneity = 0.03). A higher risk of breast cancer was found for retinol in relation to ER-/progesterone receptor-negative tumors (OR: 2.37; 95% CI: 1.20, 4.67; P-heterogeneity with ER+/progesterone receptor positive = 0.06). We observed no statistically significant interaction between smoking, alcohol, or BMI and all investigated plasma analytes (based on tertile distribution).

    Conclusion: Our results indicate that higher concentrations of plasma beta-carotene and alpha-carotene are associated with lower breast cancer risk of ER tumors.

  • 8. Bamia, Christina
    et al.
    Lagiou, Pagona
    Jenab, Mazda
    Trichopoulou, Antonia
    Fedirko, Veronika
    Aleksandrova, Krasimira
    Pischon, Tobias
    Overvad, Kim
    Olsen, Anja
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Racine, Antoine
    Kuhn, Tilman
    Boeing, Heiner
    Floegel, Anna
    Benetou, Vasiliki
    Palli, Domenico
    Grioni, Sara
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Bueno-de-Mesquita, H B As
    Dik, Vincent K
    Bhoo-Pathy, Nirmala
    Uiterwaal, Cuno S P M
    Weiderpass, Elisabete
    Lund, Eiliv
    Quirós, J Ramón
    Zamora-Ros, Raul
    Molina-Montes, Esther
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Dorronsoro, Miren
    Lindkvist, Björn
    Wallström, Peter
    Nilsson, Lena Maria
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Arctic Research Centre at Umeå University.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Khaw, Kay-Tee
    Wareham, Nick
    Bradbury, Kathryn E
    Travis, Ruth C
    Ferrari, Pietro
    Duarte-Salles, Talita
    Stepien, Magdalena
    Gunter, Marc
    Murphy, Neil
    Riboli, Elio
    Trichopoulos, Dimitrios
    Coffee, tea and decaffeinated coffee in relation to hepatocellular carcinoma in a European population: multicentre, prospective cohort study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 8, p. 1899-1908Article in journal (Refereed)
    Abstract [en]

    Inverse associations of coffee and/or tea in relation to hepatocellular carcinoma (HCC) risk have been consistently identified in studies conducted mostly in Asia where consumption patterns of such beverages differ from Europe. In the European Prospective Investigation into Cancer and nutrition (EPIC), we identified 201 HCC cases among 486,799 men/women, after a median follow-up of 11 years. We calculated adjusted hazard ratios (HRs) for HCC incidence in relation to quintiles/categories of coffee/tea intakes. We found that increased coffee and tea intakes were consistently associated with lower HCC risk. The inverse associations were substantial, monotonic and statistically significant. Coffee consumers in the highest compared to the lowest quintile had lower HCC risk by 72% [HR: 0.28; 95% confidence intervals (CIs): 0.16-0.50, p-trend < 0.001]. The corresponding association of tea with HCC risk was 0.41 (95% CI: 0.22-0.78, p-trend = 0.003). There was no compelling evidence of heterogeneity of these associations across strata of important HCC risk factors, including hepatitis B or hepatitis C status (available in a nested case-control study). The inverse, monotonic associations of coffee intake with HCC were apparent for caffeinated (p-trend = 0.009), but not decaffeinated (p-trend = 0.45) coffee for which, however, data were available for a fraction of subjects. Results from this multicentre, European cohort study strengthen the existing evidence regarding the inverse association between coffee/tea and HCC risk. Given the apparent lack of heterogeneity of these associations by HCC risk factors and that coffee/tea are universal exposures, our results could have important implications for high HCC risk subjects.

  • 9. Barrdahl, Myrto
    et al.
    Canzian, Federico
    Joshi, Amit D.
    Travis, Ruth C.
    Chang-Claude, Jenny
    Auer, Paul L.
    Gapstur, Susan M.
    Gaudet, Mia
    Diver, W. Ryan
    Henderson, Brian E.
    Haiman, Christopher A.
    Schumacher, Fredrick R.
    Le Marchand, Loic
    Berg, Christine D.
    Chanock, Stephen J.
    Hoover, Robert N.
    Rudolph, Anja
    Ziegler, Regina G.
    Giles, Graham G.
    Baglietto, Laura
    Severi, Gianluca
    Hankinson, Susan E.
    Lindstroem, Sara
    Willet, Walter
    Hunter, David J.
    Buring, Julie E.
    Lee, I-Min
    Zhang, Shumin
    Dossus, Laure
    Cox, David G.
    Khaw, Kay-Tee
    Lund, Eiliv
    Naccarati, Alessio
    Peeters, Petra H.
    Ramon Quiros, J.
    Riboli, Elio
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Trichopoulos, Dimitrios
    Prentice, Ross L.
    Kraft, Peter
    Kaaks, Rudolf
    Campa, Daniele
    Post-G WAS gene-environment interplay in breast cancer: results from the Breast and Prostate Cancer Cohort Consortium and a meta-analysis on 79 000 women2014In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 23, no 19, p. 5260-5270Article in journal (Refereed)
    Abstract [en]

    We studied the interplay between 39 breast cancer (BC) risk SNPs and established BC risk (body mass index, height, age at menarche, parity, age at menopause, smoking, alcohol and family history of BC) and prognostic factors (TNM stage, tumor grade, tumor size, age at diagnosis, estrogen receptor status and progesterone receptor status) as joint determinants of BC risk. We used a nested case-control design within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), with 16 285 BC cases and 19 376 controls. We performed stratified analyses for both the risk and prognostic factors, testing for heterogeneity for the risk factors, and case-case comparisons for differential associations of polymorphisms by subgroups of the prognostic factors. We analyzed multiplicative interactions between the SNPs and the risk factors. Finally, we also performed a meta-analysis of the interaction ORs from BPC3 and the Breast Cancer Association Consortium. After correction for multiple testing, no significant interaction between the SNPs and the established risk factors in the BPC3 study was found. The meta-analysis showed a suggestive interaction between smoking status and SLC4A7-rs4973768 (P-interaction = 8.84 x 10(-4)) which, although not significant after considering multiple comparison, has a plausible biological explanation. In conclusion, in this study of up to almost 79 000 women we can conclusively exclude any novel major interactions between genome-wide association studies hits and the epidemiologic risk factors taken into consideration, but we propose a suggestive interaction between smoking status and SLC4A7-rs4973768 that if further replicated could help our understanding in the etiology of BC.

  • 10. Barrdahl, Myrto
    et al.
    Canzian, Federico
    Lindström, Sara
    Shui, Irene
    Black, Amanda
    Hoover, Robert N
    Ziegler, Regina G
    Buring, Julie E
    Chanock, Stephen J
    Diver, W Ryan
    Gapstur, Susan M
    Gaudet, Mia M
    Giles, Graham G
    Haiman, Christopher
    Henderson, Brian E
    Hankinson, Susan
    Hunter, David J
    Joshi, Amit D
    Kraft, Peter
    Lee, I-Min
    Le Marchand, Loic
    Milne, Roger L
    Southey, Melissa C
    Willett, Walter
    Gunter, Marc
    Panico, Salvatore
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Weiderpass, Elisabete
    Sánchez, María-José
    Overvad, Kim
    Dossus, Laure
    Peeters, Petra H
    Khaw, Kay-Tee
    Trichopoulos, Dimitrios
    Kaaks, Rudolf
    Campa, Daniele
    Association of breast cancer risk loci with breast cancer survival2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 137, no 12, p. 2837-2845Article in journal (Refereed)
    Abstract [en]

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58-0.85; ptrend=2.84 x 10-4; HRheterozygotes=0.71; 95% CI: 0.55-0.92; HRhomozygotes=0.48; 95% CI: 0.31-0.76; p2DF=1.45 x 10-3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04-1.15; ptrend=6.6 x 10-4; HRheterozygotes=0.96 95% CI: 0.90-1.03; HRhomozygotes=1.21; 95% CI: 1.09-1.35; p2DF=1.25 x 10-4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662.

    What's new? Genetic factors are known to influence the risk of breast cancer, but inherited genetic variation may also affect disease prognosis and response to treatment. In this study, the we investigated whether single nucleotide polymorphisms (SNPs) that are known to be associated with breast cancer risk might also influence the survival of breast-cancer patients. While two of the investigated SNPs may influence survival, there was otherwise no indication that SNP alleles related to breast cancer risk also play a role in the survival of breast cancer patients.

  • 11. Bhangu, A
    et al.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University Hospital.
    Andersson, Linda
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University Hospital.
    Gunnarsson, Ulf
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University Hospital.
    Escobar, EG
    Mortality of emergency abdominal surgery in high-, middle- and low-income countries2016In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168, Vol. 103, no 8, p. 971-988Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Surgical mortality data are collected routinely in high-income countries, yet virtually no low- or middle-income countries have outcome surveillance in place. The aim was prospectively to collect worldwide mortality data following emergency abdominal surgery, comparing findings across countries with a low, middle or high Human Development Index (HDI).

    METHODS: This was a prospective, multicentre, cohort study. Self-selected hospitals performing emergency surgery submitted prespecified data for consecutive patients from at least one 2-week interval during July to December 2014. Postoperative mortality was analysed by hierarchical multivariable logistic regression.

    RESULTS: Data were obtained for 10 745 patients from 357 centres in 58 countries; 6538 were from high-, 2889 from middle- and 1318 from low-HDI settings. The overall mortality rate was 1·6 per cent at 24 h (high 1·1 per cent, middle 1·9 per cent, low 3·4 per cent; P < 0·001), increasing to 5·4 per cent by 30 days (high 4·5 per cent, middle 6·0 per cent, low 8·6 per cent; P < 0·001). Of the 578 patients who died, 404 (69·9 per cent) did so between 24 h and 30 days following surgery (high 74·2 per cent, middle 68·8 per cent, low 60·5 per cent). After adjustment, 30-day mortality remained higher in middle-income (odds ratio (OR) 2·78, 95 per cent c.i. 1·84 to 4·20) and low-income (OR 2·97, 1·84 to 4·81) countries. Surgical safety checklist use was less frequent in low- and middle-income countries, but when used was associated with reduced mortality at 30 days.

    CONCLUSION: Mortality is three times higher in low- compared with high-HDI countries even when adjusted for prognostic factors. Patient safety factors may have an important role.

  • 12. Bhoo-Pathy, Nirmala
    et al.
    Uiterwaal, Cuno S. P. M.
    Dik, Vincent K.
    Jeurnink, Suzanne M.
    Bech, Bodil H.
    Overvad, Kim
    Halkjær, Jytte
    Tjønneland, Anne
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Racine, Antoine
    Katzke, Verena A.
    Li, Kuanrong
    Boeing, Heiner
    Floegel, Anna
    Androulidaki, Anna
    Bamia, Christina
    Trichopoulou, Antonia
    Masala, Giovanna
    Panico, Salvatore
    Crosignani, Paolo
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H. M.
    Gavrilyuk, Oxana
    Skeie, Guri
    Weiderpass, Elisabete
    Duell, Eric J.
    Arguelles, Marcial
    Molina-Montes, Esther
    Navarro, Carmen
    Ardanaz, Eva
    Dorronsoro, Miren
    Lindkvist, Björn
    Wallström, Peter
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ye, Weimin
    Umeå University, Faculty of Medicine, Department of Biobank Research. Karolinska institutet.
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J.
    Travis, Ruth C.
    Duarte-Salles, Talita
    Freisling, Heinz
    Licaj, Idlir
    Gallo, Valentina
    Michaud, Dominique S.
    Riboli, Elio
    Bueno-de-Mesquita, H. Bas
    Intake of Coffee, Decaffeinated Coffee, or Tea Does Not Affect Risk for Pancreatic Cancer: Results From the European Prospective Investigation into Nutrition and Cancer Study2013In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 11, no 11, p. 1486-1492Article in journal (Refereed)
    Abstract [en]

    BACKGROUND & AIMS: Few modifiable risk factors have been implicated in the etiology of pancreatic cancer. There is little evidence for the effects of caffeinated coffee, decaffeinated coffee, or tea intake on risk of pancreatic cancer. We investigated the association of total coffee, caffeinated coffee, decaffeinated coffee, and tea consumption with risk of pancreatic cancer.

    METHODS: This study was conducted within the European Prospective Investigation into Nutrition and Cancer cohort, comprising male and female participants from 10 European countries. Between 1992 and 2000, there were 477,312 participants without cancer who completed a dietary questionnaire, and were followed up to determine pancreatic cancer incidence. Coffee and tea intake was calibrated with a 24-hour dietary recall. Adjusted hazard ratios (HRs) were computed using multivariable Cox regression.

    RESULTS: During a mean follow-up period of 11.6 y, 865 first incidences of pancreatic cancers were reported. When divided into fourths, neither total intake of coffee (HR, 1.03; 95% confidence interval [CI], 0.83-1.27; high vs low intake), decaffeinated coffee (HR, 1.12; 95% CI, 0.76-1.63; high vs low intake), nor tea were associated with risk of pancreatic cancer (HR, 1.22, 95% CI, 0.95-1.56; high vs low intake). Moderately low intake of caffeinated coffee was associated with an increased risk of pancreatic cancer (HR, 1.33; 95% CI, 1.02-1.74), compared with low intake. However, no graded dose response was observed, and the association attenuated after restriction to histologically confirmed pancreatic cancers.

    CONCLUSIONS: Based on an analysis of data from the European Prospective Investigation into Nutrition and Cancer cohort, total coffee, decaffeinated coffee, and tea consumption are not related to the risk of pancreatic cancer.

  • 13. Campa, Daniele
    et al.
    Barrdahl, Myrto
    Gaudet, Mia M.
    Black, Amanda
    Chanock, Stephen J.
    Diver, W. Ryan
    Gapstur, Susan M.
    Haiman, Christopher
    Hankinson, Susan
    Hazra, Aditi
    Henderson, Brian
    Hoover, Robert N.
    Hunter, David J.
    Joshi, Amit D.
    Kraft, Peter
    Le Marchand, Loic
    Lindstrom, Sara
    Willett, Walter
    Travis, Ruth C.
    Amiano, Pilar
    Siddiq, Afshan
    Trichopoulos, Dimitrios
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Tjonneland, Anne
    Weiderpass, Elisabete
    Peeters, Petra H.
    Panico, Salvatore
    Dossus, Laure
    Ziegler, Regina G.
    Canzian, Federico
    Kaaks, Rudolf
    Genetic risk variants associated with in situ breast cancer2015In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 17, article id 82Article in journal (Refereed)
    Abstract [en]

    Introduction: Breast cancer in situ (BCIS) diagnoses, a precursor lesion for invasive breast cancer, comprise about 20 % of all breast cancers (BC) in countries with screening programs. Family history of BC is considered one of the strongest risk factors for BCIS.

    Methods: To evaluate the association of BC susceptibility loci with BCIS risk, we genotyped 39 single nucleotide polymorphisms (SNPs), associated with risk of invasive BC, in 1317 BCIS cases, 10,645 invasive BC cases, and 14,006 healthy controls in the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3). Using unconditional logistic regression models adjusted for age and study, we estimated the association of SNPs with BCIS using two different comparison groups: healthy controls and invasive BC subjects to investigate whether BCIS and BC share a common genetic profile.

    Results: We found that five SNPs (CDKN2BAS-rs1011970, FGFR2-rs3750817, FGFR2-rs2981582, TNRC9-rs3803662, 5p12-rs10941679) were significantly associated with BCIS risk (P value adjusted for multiple comparisons <0.0016). Comparing invasive BC and BCIS, the largest difference was for CDKN2BAS-rs1011970, which showed a positive association with BCIS (OR = 1.24, 95 % CI: 1.11-1.38, P = 1.27 x 10(-4)) and no association with invasive BC (OR = 1.03, 95 % CI: 0.99-1.07, P = 0.06), with a P value for case-case comparison of 0.006. Subgroup analyses investigating associations with ductal carcinoma in situ (DCIS) found similar associations, albeit less significant (OR = 1.25, 95 % CI: 1.09-1.42, P = 1.07 x 10(-3)). Additional risk analyses showed significant associations with invasive disease at the 0.05 level for 28 of the alleles and the OR estimates were consistent with those reported by other studies.

    Conclusions: Our study adds to the knowledge that several of the known BC susceptibility loci are risk factors for both BCIS and invasive BC, with the possible exception of rs1011970, a putatively functional SNP situated in the CDKN2BAS gene that may be a specific BCIS susceptibility locus.

  • 14. Campa, Daniele
    et al.
    Barrdahl, Myrto
    Tsilidis, Konstantinos K
    Severi, Gianluca
    Diver, W Ryan
    Siddiq, Afshan
    Chanock, Stephen
    Hoover, Robert N
    Ziegler, Regina G
    Berg, Christine D
    Buys, Saundra S
    Haiman, Christopher A
    Henderson, Brian E
    Schumacher, Fredrick R
    Le Marchand, Loic
    Flesch-Janys, Dieter
    Lindstroem, Sara
    Hunter, David J
    Hankinson, Susan E
    Willett, Walter C
    Kraft, Peter
    Cox, David G
    Khaw, Kay-Tee
    Tjonneland, Anne
    Dossus, Laure
    Trichopoulos, Dimitrios
    Panico, Salvatore
    van Gils, Carla H
    Weiderpass, Elisabete
    Barricarte, Aurelio
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Gaudet, Mia M
    Giles, Graham
    Southey, Melissa
    Baglietto, Laura
    Chang-Claude, Jenny
    Kaaks, Rudolf
    Canzian, Federico
    A genome-wide "pleiotropy scan'' does not identify new susceptibility loci for estrogen receptor negative breast cancer2014In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 2, p. e85955-Article in journal (Refereed)
    Abstract [en]

    Approximately 15-30% of all breast cancer tumors are estrogen receptor negative (ER-). Compared with ER- positive (ER+) disease they have an earlier age at onset and worse prognosis. Despite the vast number of risk variants identified for numerous cancer types, only seven loci have been unambiguously identified for ER- negative breast cancer. With the aim of identifying new susceptibility SNPs for this disease we performed a pleiotropic genome-wide association study (GWAS). We selected 3079 SNPs associated with a human complex trait or disease at genome-wide significance level (P<5x10(-8)) to perform a secondary analysis of an ER- negative GWAS from the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium (BPC3), including 1998 cases and 2305 controls from prospective studies. We then tested the top ten associations (i.e. with the lowest P-values) using three additional populations with a total sample size of 3509 ER+ cases, 2543 ER- cases and 7031 healthy controls. None of the 3079 selected variants in the BPC3 ER- GWAS were significant at the adjusted threshold. 186 variants were associated with ER- breast cancer risk at a conventional threshold of P<0.05, with P-values ranging from 0.049 to 2.3 x 10(-4). None of the variants reached statistical significance in the replication phase. In conclusion, this study did not identify any novel susceptibility loci for ER-breast cancer using a "pleiotropic approach''.

  • 15. Campa, Daniele
    et al.
    Claus, Rainer
    Dostal, Lucie
    Stein, Angelika
    Chang-Claude, Jenny
    Meidtner, Karina
    Boeing, Heiner
    Olsen, Anja
    Tjønneland, Anne
    Overvad, Kim
    Rodríguez, Laudina
    Bonet, Catalina
    Sánchez, Maria-José
    Amiano, Pilar
    Huerta, José María
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C
    Allen, Naomi E
    Trichopoulou, Antonia
    Bamia, Christina
    Benetou, Vassiliki
    Palli, Domenico
    Agnoli, Claudia
    Panico, Salvatore
    Tumino, Rosario
    Sacerdote, Carlotta
    van Kranen, Henk
    Bas Bueno-de-Mesquita, H
    Peeters, Petra H M
    van Gils, Carla H
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lund, Eiliv
    Gram, Inger Torhild
    Rinaldi, Sabina
    Chajes, Veronique
    Romieu, Isabelle
    Engel, Pierre
    Boutron-Ruault, Marie Christine
    Clavel-Chapelon, Françoise
    Siddiq, Afshan
    Riboli, Elio
    Canzian, Federico
    Kaaks, Rudolf
    Variation in genes coding for AMP-activated protein kinase (AMPK) and breast cancer risk in the European Prospective Investigation on Cancer (EPIC).2011In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 127, no 3, p. 761-767Article in journal (Refereed)
    Abstract [en]

    AMP-activated protein kinase (AMPK) is an energy sensing/signalling intracellular protein which is activated by an increase in the cellular AMP:ATP ratio after ATP depletion. Once activated, AMPK inhibits fatty acid synthesis and the Akt-mTOR pathway, and activates the p53-p21 axis. All these molecular mechanisms are thought to play a key role in breast carcinogenesis. We investigated the genetic variability of four genes encoding AMPK (PRKAA1, PRKAA2, PRKAB1 and PRKAB2). Using a tagging approach and selecting SNPs we covered all the common genetic variation of these genes. We tested association of tagging SNPs in our four candidate genes with breast cancer (BC) risk in a study of 1340 BC cases and 2536 controls nested into the European Prospective Investigation into Cancer and Nutrition (EPIC). Given the relevance of AMPK on fatty acid synthesis and the importance of body fatness as a BC risk factor, we tested association of SNPs and body-mass index as well. We observed no statistically significant association between the SNPs in the PRKAs genes and BC risk and BMI after correction for multiple testing.

  • 16. Campa, Daniele
    et al.
    Mergarten, Bjoern
    De Vivo, Immaculata
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Severi, Gianluca
    Nieters, Alexandra
    Katzke, Verena A.
    Trichopoulou, Antonia
    Yiannakouris, Nikos
    Trichopoulos, Dimitrios
    Boeing, Heiner
    Ramon Quiros, J.
    Duell, Eric J.
    Molina-Montes, Esther
    Mara Huerta, Jose
    Ardanaz, Eva
    Dorronsoro, Miren
    Khaw, Kay-Tee
    Wareham, Nicholas
    Travis, Ruth C.
    Palli, Domenico
    Pala, Valeria
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Vineis, Paolo
    Riboli, Elio
    Siddiq, Afshan
    Bueno-de-Mesquita, H. B.
    Peeters, Petra H.
    Nilsson, Peter M.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ye, Weimin
    Umeå University, Faculty of Medicine, Department of Biobank Research. Karolinska Inst, Dept Med Epidemiol & Biostat.
    Lund, Eiliv
    Jareid, Mie
    Weiderpass, Elisabete
    Duarte-Salles, Talita
    Kong, So Yeon
    Stepien, Magdalena
    Canzian, Federico
    Kaaks, Rudolf
    Leukocyte Telomere Length in Relation to Pancreatic Cancer Risk: A Prospective Study2014In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, no 11, p. 2447-2454Article in journal (Refereed)
    Abstract [en]

    Background: Several studies have examined leukocyte telomere length (LTL) as a possible predictor for cancer at various organ sites. The hypothesis originally motivating many of these studies was that shorter telomeres would be associated with an increase in cancer risk; the results of epidemiologic studies have been inconsistent, however, and suggested positive, negative, or null associations. Two studies have addressed the association of LTL in relation to pancreatic cancer risk and the results are contrasting. Methods: We measured LTL in a prospective study of 331 pancreatic cancer cases and 331 controls in the context of the European Prospective Investigation into Cancer and Nutrition (EPIC). Results: We observed that the mean LTL was higher in cases (0.59 +/- 0.20) than in controls (0.57 +/- 0.17), although this difference was not statistically significant (P = 0.07), and a basic logistic regression model showed no association of LTL with pancreas cancer risk. When adjusting for levels of HbA1c and C-peptide, however, there was a weakly positive association between longer LTL and pancreatic cancer risk [OR, 1.13; 95% confidence interval (CI), 1.01-1.27]. Additional analyses by cubic spline regression suggested a possible nonlinear relationship between LTL and pancreatic cancer risk (P = 0.022), with a statistically nonsignificant increase in risk at very low LTL, as well as a significant increase at high LTL. Conclusion: Taken together, the results from our study do not support LTL as a uniform and strong predictor of pancreatic cancer. Impact: The results of this article can provide insights into telomere dynamics and highlight the complex relationship between LTL and pancreatic cancer risk.

  • 17. Chuang, Shu-Chun
    et al.
    Stolzenberg-Solomon, Rachael
    Ueland, Per Magne
    Vollset, Stein Emil
    Midttun, Oivind
    Olsen, Anja
    Tjonneland, Anne
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Clavel-Chapelon, Francoise
    Teucher, Birgit
    Kaaks, Rudolf
    Weikert, Cornelia
    Boeing, Heiner
    Trichopoulou, Antonia
    Benetou, Vassiliki
    Naska, Androniki
    Jenab, Mazda
    Slimani, Nadia
    Romieu, Isabelle
    Michaud, Dominique S.
    Palli, Domenico
    Sieri, Sabina
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Skeie, Guri
    Duell, Eric J.
    Rodriguez, Laudina
    Molina-Montes, Esther
    Maria Huerta, Jose
    Larranaga, Nerea
    Barricarte Gurrea, Aurelio
    Johansen, Dorthe
    Manjer, Jonas
    Ye, Weimin
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Peeters, Petra H. M.
    Jeurnink, Suzanne
    Wareham, Nicholas
    Khaw, Kay-Tee
    Crowe, Francesca
    Riboli, Elio
    Bueno-de-Mesquita, Bas
    Vineis, Paolo
    A U-shaped relationship between plasma folate and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition2011In: European Journal of Cancer, ISSN 0959-8049, E-ISSN 1879-0852, Vol. 47, no 12, p. 1808-1816Article in journal (Refereed)
    Abstract [en]

    Folate intake has shown an inverse association with pancreatic cancer; nevertheless, results from plasma measurements were inconsistent. The aim of this study is to examine the association between plasma total homocysteine, methionine, folate, cobalamin, pyridoxal 5'-phosphate, riboflavin, flavin mononucleotide and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC). We conducted a nested case-control study in the EPIC cohort, which has an average of 9.6 years of follow-up (1992-2006), using 463 incident pancreatic cancer cases. Controls were matched to each case by center, sex, age (+/- 1 year), date (+/- 1 year) and time (+/- 3 h) at blood collection and fasting status. Conditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (CI), adjusting for education, smoking status, plasma cotinine concentration, alcohol drinking, body mass index and diabetes status. We observed a U-shaped association between plasma folate and pancreatic cancer risk. The ORs for plasma folate <= 5, 5-10, 10-15 (reference), 15-20, and > 20 nmol/L were 1.58 (95% CI = 0.72-3.46), 1.39 (0.93-2.08), 1.0 (reference), 0.79 (0.52-1.21), and 1.34 (0.89-2.02), respectively. Methionine was associated with an increased risk in men (per quintile increment: OR = 1.17, 95% CI = 1.00-1.38) but not in women (OR = 0.91, 95% CI = 0.78-1.07; p for heterogeneity < 0.01). Our results suggest a U-shaped association between plasma folate and pancreatic cancer risk in both men and women. The positive association that we observed between methionine and pancreatic cancer may be sex dependent and may differ by time of follow-up. However, the mechanisms behind the observed associations warrant further investigation.

  • 18. Clendenen, Tess V.
    et al.
    Ge, Wenzhen
    Koenig, Karen L.
    Axelsson, Tomas
    Liu, Mengling
    Afanasyeva, Yelena
    Andersson, Anne
    Arslan, Alan A.
    Chen, Yu
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lenner, Per
    Kirchhoff, Tomas
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Shore, Roy E.
    Sund, Malin
    Zeleniuch-Jacquotte, Anne
    Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: a nested case-control study2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0140478Article in journal (Refereed)
    Abstract [en]

    Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH) D concentration in GWAS were also associated with plasma 25(OH) D in our study (p-trend < 0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH) D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.

  • 19. Companioni, Osmel
    et al.
    Bonet, Catalina
    Muñoz, Xavier
    Weiderpass, Elisabete
    Panico, Salvatore
    Tumino, Rosario
    Palli, Domenico
    Agnoli, Claudia
    Vineis, Paolo
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Clavel-Chapelon, Françoise
    Travis, Ruth C
    Khaw, Kay-Tee
    Riboli, Elio
    Murphy, Neil
    Vergnaud, Anne-Claire
    Trichopoulou, Antonia
    Benetou, Vassiliki
    Trichopoulos, Dimitrios
    Lund, Eiliv
    Johansen, Dorthe
    Lindkvist, Björn
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research. International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ardanaz, Eva
    Sánchez-Cantalejo, Emilio
    Huerta, Jose M
    Dorronsoro, Miren
    Quirós, José Ramón
    Tjonneland, Anne
    Mortensen, Lotte Maxild
    Overvad, Kim
    Chang-Claude, Jenny
    Rizzato, Cosmeri
    Boeing, Heiner
    de Mesquita, H Bas Bueno
    Siersema, Peter
    Peeters, Petra Hm
    Numans, Mattijs E
    Carneiro, Fatima
    Licaj, Idlir
    Freisling, Heinz
    Sala, Núria
    González, Carlos A
    Polymorphisms of H. pylori signaling pathway genes and gastric cancer risk in the European EPIC-eurgast cohort2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 1, p. 92-101Article in journal (Refereed)
    Abstract [en]

    Helicobacter pylori is a recognized causal factor of noncardia gastric cancer (GC). Lipopolysaccaride and peptidoglycan of this bacterium are recognized by CD14, TLR4 and NOD2 human proteins, while NFKB1 activates the transcription of pro-inflammatory cytokines to elicit an immune response. SNPs in these genes have been associated with GC in different populations. We genotyped 30 SNPs of these genes, in 365 gastric adenocarcinomas and 1284 matched controls from the EPIC cohort. The association with GC and its histological and anatomical subtypes was analyzed by logistic regression and corrected for multiple comparisons. Using a log-additive model we found a significant association between SNPs in CD14, NOD2 and TLR4 with GC risk. However, after applying the multiple comparisons tests only the NOD2 region remained significant (p=0.009). Analysis according to anatomical subtypes revealed NOD2 and NFKB1 SNPs associated with noncardia GC and CD14 SNPs associated with cardia GC, while analysis according to histological subtypes showed that CD14 was associated with intestinal but not diffuse GC. The multiple comparisons tests confirmed the association of NOD2 with noncardia GC (p=0.0003) and CD14 with cardia GC (p=0.01). Haplotype analysis was in agreement with single SNP results for NOD2 and CD14 genes. From these results we conclude that genetic variation in NOD2 associates with noncardia GC while variation in CD14 is associated with cardia GC.

  • 20. de Boniface, Jana
    et al.
    Frisell, Jan
    Andersson, Yvette
    Bergkvist, Leif
    Ahlgren, Johan
    Ryden, Lisa
    Bagge, Roger Olofsson
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences. Surgery Center, Norrland University Hospital, Umeå, Sweden.
    Johansson, Hemming
    Lundstedt, Dan
    Survival and axillary recurrence following sentinel node-positive breast cancer without completion axillary lymph node dissection: the randomized controlled SENOMAC trial2017In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 17, article id 379Article in journal (Refereed)
    Abstract [en]

    Background: The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference.

    Methods: The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1:1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years.

    Discussion: Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.

  • 21. Del Chiaro, Marco
    et al.
    Besselink, Marc G.
    Scholten, Lianne
    Bruno, Marco J.
    Cahen, Djuna L.
    Gress, Thomas M.
    van Hooft, Jeanin E.
    Lerch, Markus M.
    Mayerle, Julia
    Hackert, Thilo
    Satoi, Sohei
    Zerbi, Alessandro
    Cunningham, David
    De Angelis, Claudio
    Giovanni, Marc
    de-Madaria, Enrique
    Hegyi, Peter
    Rosendahl, Jonas
    Friess, Helmut
    Manfredi, Riccardo
    Levy, Philippe
    Real, Francisco X.
    Sauvanet, Alain
    Abu Hilal, Mohammed
    Marchegiani, Giovanni
    Esposito, Irene
    Ghaneh, Paula
    Engelbrecht, Marc R. W.
    Fockens, Paul
    van Huijgevoort, Nadine C. M.
    Wolfgang, Christopher
    Bassi, Claudio
    Gubergrits, Natalya B.
    Verbeke, Caroline
    Kloppel, Gunter
    Scarpa, Aldo
    Zamboni, Giuseppe
    Lennon, Anne Marie
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Kartalis, Nikolaos
    Grenacher, Lars
    Falconi, Massimo
    Arnelo, Urban
    Kopchak, Kostantin V.
    Oppong, Kofi
    McKay, Colin
    Hauge, Truls
    Conlon, Kevin
    Adham, Mustapha
    Ceyhan, Guralp O.
    Salvia, Roberto
    Dervenis, Christos
    Allen, Peter
    Paye, Francois
    Bartsch, Detlef K.
    Lohr, Matthias
    Mutignani, Massimiliano
    Laukkarinen, Johanna
    Schulick, Richard
    Valente, Roberto
    Seufferlein, Thomas
    Capurso, Gabriele
    Siriwardena, Ajith
    Neoptolemos, John P.
    Pukitis, Aldis
    Segersvard, Ralf
    Aghdassi, A.
    Andrianello, S.
    Bossuyt, P.
    Bulow, R.
    Cardenas-Jaen, K.
    Cortegoso, P.
    Fontana, M.
    Haeberle, L.
    Heckler, M.
    Litvin, A.
    Mann, K.
    Michalski, C.
    Michl, P.
    Nappo, G.
    Perri, G.
    Persson, S.
    Scheufele, F.
    Sclafani, F.
    Schmidt, M.
    Venezia, L.
    Volker, F.
    Vullierm, M-P
    Wusten, L.
    European evidence-based guidelines on pancreatic cystic neoplasms2018In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 67, no 5, p. 789-804Article in journal (Refereed)
    Abstract [en]

    Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring < 40 mm without an enhancing nodule. Relative indications for surgery in IPMN include a main pancreatic duct (MPD) diameter between 5 and 9.9 mm or a cyst diameter >= 40 mm. Absolute indications for surgery in IPMN, due to the high-risk of malignant transformation, include jaundice, an enhancing mural nodule > 5 mm, and MPD diameter > 10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

  • 22. Duell, Eric J.
    et al.
    Travier, Noemie
    Lujan-Barroso, Leila
    Dossus, Laure
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Tumino, Rosario
    Masala, Giovanna
    Krogh, Vittorio
    Panico, Salvatore
    Ricceri, Fulvio
    Luisa Redondo, Maria
    Dorronsoro, Miren
    Molina-Montes, Esther
    Huerta, Jose M.
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick J.
    Allen, Naomi E.
    Travis, Ruth
    Siersema, Peter D.
    Peeters, Petra H. M.
    Trichopoulou, Antonia
    Fragogeorgi, Eirini
    Oikonomou, Eleni
    Boeing, Heiner
    Schuetze, Madlen
    Canzian, Federico
    Lukanova, Annekatrin
    Tjonneland, Anne
    Roswall, Nina
    Overvad, Kim
    Weiderpass, Elisabete
    Gram, Inger Torhild
    Lund, Eiliv
    Lindkvist, Bjorn
    Johansen, Dorthe
    Ye, Weimin
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Fedirko, Veronika
    Jenab, Mazda
    Michaud, Dominique S.
    Riboli, Elio
    Bueno-de-Mesquita, H. Bas
    Menstrual and reproductive factors in women, genetic variation in CYP17A1, and pancreatic cancer risk in the European prospective investigation into cancer and nutrition (EPIC) cohort2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 132, no 9, p. 2164-2175Article in journal (Refereed)
    Abstract [en]

    Menstrual and reproductive factors and exogenous hormone use have been investigated as pancreatic cancer risk factors in case-control and cohort studies, but results have been inconsistent. We conducted a prospective examination of menstrual and reproductive factors, exogenous hormone use and pancreatic cancer risk (based on 304 cases) in 328,610 women from the EPIC cohort. Then, in a case-control study nested within the EPIC cohort, we examined 12 single nucleotide polymorphisms (SNPs) in CYP17A1 (an essential gene in sex steroid metabolism) for association with pancreatic cancer in women and men (324 cases and 353 controls). Of all factors analyzed, only younger age at menarche (<12 vs. 13 years) was moderately associated with an increased risk of pancreatic cancer in the full cohort; however, this result was marginally significant (HR = 1.44; 95% CI = 0.992.10). CYP17A1 rs619824 was associated with HRT use (p value = 0.037) in control women; however, none of the SNPs alone, in combination, or as haplotypes were associated with pancreatic cancer risk. In conclusion, with the possible exception of an early age of menarche, none of the menstrual and reproductive factors, and none of the 12 common genetic variants we evaluated at the CYP17A1 locus makes a substantial contribution to pancreatic cancer susceptibility in the EPIC cohort.

  • 23. Ekelund, Ulf
    et al.
    Ward, Heather A.
    Norat, Teresa
    Luan, Jian'an
    May, Anne M.
    Weiderpass, Elisabete
    Sharp, Stephen J.
    Overvad, Kim
    Ostergaard, Jane Nautrup
    TjOnneland, Anne
    Johnsen, Nina Fons
    Mesrine, Sylvie
    Foamier, Agnes
    Fagherazzi, Guy
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Li, Kuanrong
    Kaaks, Rudolf
    Ferrari, Pietro
    Licaj, Idlir
    Jenab, Mazda
    Bergmann, Manuela
    Boeing, Heiner
    Palli, Domenico
    Sieri, Sabina
    Panico, Salvatore
    Tumino, Rosario
    Vineis, Paolo
    Peeters, Petra H.
    Monnikhof, Evelyn
    Bueno-de-Mesquita, H. Bas
    Ramon Quiros, J.
    Agudo, Antonio
    Sanchez, Maria-Jose
    Maria Huerta, Jose
    Ardanaz, Eva
    Arriola, Larraitz
    Hedblad, Bo
    Wirfalt, Elisabet
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. International Agency for Research on Cancer (IARC), Lyon, France.
    Key, Timothy J.
    Travis, Ruth C.
    Khaw, Kay-Tee
    Brage, Soren
    Wareham, Nicholas J.
    Riboli, Elio
    Physical activity and all-cause mortality across levels of overall and abdominal adiposity in European men and women: the European Prospective Investigation into Cancer and Nutrition Study (EPIC)2015In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 101, no 3, p. 613-621Article in journal (Refereed)
    Abstract [en]

    Background: The higher risk of death resulting from excess adiposity may be attenuated by physical activity (PA). However, the theoretical number of deaths reduced by eliminating physical inactivity compared with overall and abdominal obesity remains unclear.

    Objective: We examined whether overall and abdominal adiposity modified the association between PA and all-cause mortality and estimated the population attributable fraction (PAF) and the years of life gained for these exposures.

    Design: This was a cohort study in 334,161 European men and women. The mean follow-up time was 12.4 y, corresponding to 4,154,915 person-years. Height, weight, and waist circumference (WC) were measured in the clinic. PA was assessed with a validated self-report instrument. The combined associations between PA, BMI, and WC with mortality were examined with Cox proportional hazards models, stratified by center and age group, and adjusted for sex, education, smoking, and alcohol intake. Center-specific PAF associated with inactivity, body mass index (BMI; in kg/m(2)) (>30), and WC (>= 102 cm for men, >= 88 cm for women) were calculated and combined in random-effects meta-analysis. Life-tables analyses were used to estimate gains in life expectancy for the exposures.

    Results: Significant interactions (PA x BMI and PA x WC) were observed, so HRs were estimated within BMI and WC strata. The hazards of all-cause mortality were reduced by 16-30% in moderately inactive individuals compared with those categorized as inactive in different strata of BMI and WC. Avoiding all inactivity would theoretically reduce all-cause mortality by 7.35% (95% CI: 5.88%, 8.83%). Corresponding estimates for avoiding obesity (BMI >30) were 3.66% (95% CI: 2.30%, 5.01%). The estimates for avoiding high WC were similar to those for physical inactivity.

    Conclusion: The greatest reductions in mortality risk were observed between the 2 lowest activity groups across levels of general and abdominal adiposity, which suggests that efforts to encourage even small increases in activity in inactive individuals may be beneficial to public health.

  • 24. Emaus, Marleen J.
    et al.
    van Gils, Carla H.
    Bakker, Marije F.
    Bisschop, Charlotte N. Steins
    Monninkhof, Evelyn M.
    Bueno-de-Mesquita, H. B(as)
    Travier, Noemie
    Berentzen, Tina Landsvig
    Overvad, Kim
    Tjonneland, Anne
    Romieu, Isabelle
    Rinaldi, Sabina
    Chajes, Veronique
    Gunter, Marc J.
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Mesrine, Sylvie
    Chang-Claude, Jenny
    Kaaks, Rudolf
    Boeing, Heiner
    Aleksandrova, Krasimira
    Trichopoulou, Antonia
    Naska, Androniki
    Orfanos, Philippos
    Palli, Domenico
    Agnoli, Claudia
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Braaten, Tonje
    Borch, Kristin Benjaminsen
    Lund, Eiliv
    Menendez, Virginia
    Sanchez, Maria-Jose
    Navarro, Carmen
    Barricarte, Aurelio
    Amiano, Pilar
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Andersson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Borgquist, Signe
    Olsson, Asa
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C.
    Riboli, Elio
    Peeters, Petra H. M.
    May, Anne M.
    Weight change in middle adulthood and breast cancer risk in the EPIC-PANACEA study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 12, p. 2887-2899Article in journal (Refereed)
    Abstract [en]

    Long-term weight gain (i.e., weight gain since age 20) has been related to higher risk of postmenopausal breast cancer, but a lower risk of premenopausal breast cancer. The effect of weight change in middle adulthood is unclear. We investigated the association between weight change in middle adulthood (i.e., women aged 40-50 years) and the risk of breast cancer before and after the age of 50. We included female participants of the European Prospective Investigation into Cancer and Nutrition cohort, with information on anthropometric measures at recruitment and after a median follow-up of 4.3 years. Annual weight change was categorized using quintiles taking quintile 2 and 3 as the reference category (-0.44 to 0.36 kg/year). Multivariable Cox proportional hazards regression analysis was used to examine the association. 205,723 women were included and 4,663 incident breast cancer cases were diagnosed during a median follow-up of 7.5 years (from second weight assessment onward). High weight gain (Q5: 0.83-4.98 kg/year) was related to a slightly, but significantly higher breast cancer risk (HRQ5_versus_Q2/3: 1.09, 95% CI: 1.01-1.18). The association was more pronounced for breast cancer diagnosed before or at age 50 (HRQ5_versus_Q2/3: 1.37, 95% CI: 1.02-1.85). Weight loss was not associated with breast cancer risk. There was no evidence for heterogeneity by hormone receptor status. In conclusion, high weight gain in middle adulthood increases the risk of breast cancer. The association seems to be more pronounced for breast cancer diagnosed before or at age 50. Our results illustrate the importance of avoiding weight gain in middle adulthood.

  • 25. Espinosa-Parrilla, Yolanda
    et al.
    Munoz, Xavier
    Bonet, Catalina
    Garcia, Nadia
    Vencesla, Adoracion
    Yiannakouris, Nikos
    Naccarati, Alessio
    Sieri, Sabina
    Panico, Salvatore
    Huerta, Jose M.
    Barricarte, Aurelio
    Menendez, Virginia
    Sanchez-Cantalejo, Emilio
    Dorronsoro, Miren
    Brennan, Paul
    Duarte-Salles, Talita
    Bueno-de-Mesquita, H. B. (As)
    Weiderpass, Elisabete
    Lund, Eiliv
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Numans, Mattijs E.
    Tumino, Rosario
    Canzian, Federico
    Campa, Daniele
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Johansson, Mattias
    Umeå University, Faculty of Medicine, Department of Biobank Research. International Agency for Research on Cancer (IARC-WHO), Lyon, France.
    Ohlsson, Bodil
    Lindkvist, Bjorn
    Overvad, Kim
    Tjonneland, Anne
    Palli, Domenico
    Travis, Ruth C.
    Khaw, Kay-Tee
    Wareham, Nick
    Boeing, Heiner
    Nesi, Gabriella
    Riboli, Elio
    Gonzalez, Carlos A.
    Sala, Nuria
    Genetic association of gastric cancer with miRNA clusters including the cancer-related genes MIR29, MIR25, MIR93 and MIR106: Results from the EPIC-EURGAST study2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 135, no 9, p. 2065-2076Article in journal (Refereed)
    Abstract [en]

    MicroRNAs (miRNAs) are post-transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single-nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log-additive model. Furthermore, several of these miRNAs passed the gene-based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR-29a/miR-29b-1 cluster were associated with diffuse subtype (minimum p-value=1.7 x 10(-4); odds ratio, OR=1.72; 95% confidence interval, CI=1.30-2.28), two tagSNPs of the miR-25/miR-93/miR-106b cluster were associated with cardia GC (minimum p-value=5.38 x 10(-3); OR=0.56, 95% CI=0.37-0.86) and one tagSNP of the miR-363/miR-92a-2/miR-19b-2/miR-20b/miR-18b/miR-106a cluster was associated with noncardia GC (minimum p-value=5.40 x 10(-3); OR=1.41, 95% CI=1.12-1.78). Some functionally validated target genes of these miRNAs are implicated in cancer-related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.

  • 26. Fedirko, V.
    et al.
    Lukanova, A.
    Bamia, C.
    Trichopolou, A.
    Trepo, E.
    Noethlings, U.
    Schlesinger, S.
    Aleksandrova, K.
    Boffetta, P.
    Tjonneland, A.
    Johnsen, N. F.
    Overvad, K.
    Fagherazzi, G.
    Racine, A.
    Boutron-Ruault, M. C.
    Grote, V.
    Kaaks, R.
    Boeing, H.
    Naska, A.
    Adarakis, G.
    Valanou, E.
    Palli, D.
    Sieri, S.
    Tumino, R.
    Vineis, P.
    Panico, S.
    Bueno-de-Mesquita, H. B(as).
    Siersema, P. D.
    Peeters, P. H.
    Weiderpass, E.
    Skeie, G.
    Engeset, D.
    Quiros, J. R.
    Zamora-Ros, R.
    Sanchez, M. J.
    Amiano, P.
    Huerta, J. M.
    Barricarte, A.
    Johansen, D.
    Lindkvist, B.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Crowe, F.
    Khaw, K. T.
    Ferrari, P.
    Romieu, I.
    Chuang, S. C.
    Riboli, E.
    Jenab, M.
    Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 2, p. 543-553Article in journal (Refereed)
    Abstract [en]

    The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.

  • 27. Fedirko, V
    et al.
    Trichopolou, A
    Bamia, C
    Duarte-Salles, T
    Trepo, E
    Aleksandrova, K
    Nöthlings, U
    Lukanova, A
    Lagiou, P
    Boffetta, P
    Trichopoulos, D
    Katzke, VA
    Overvad, K
    Tjønneland, A
    Hansen, L
    Boutron-Ruault, MC
    Fagherazzi, G
    Bastide, N
    Panico, S
    Grioni, S
    Vineis, P
    Palli, D
    Tumino, R
    Bueno-de-Mesquita, HB
    Peeters, PH
    Skeie, G
    Engeset, D
    Parr, CL
    Jakszyn, P
    Sánchez, MJ
    Barricarte, A
    Amiano, P
    Chirlaque, M
    Quirós, JR
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sonestedt, E
    Ericson, U
    Key, TJ
    Khaw, KT
    Ferrari, P
    Romieu, I
    Riboli, E
    Jenab, M
    Consumption of fish and meats and risk of hepatocellular carcinoma: the European Prospective Investigation into Cancer and Nutrition (EPIC)2013In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 24, no 8, p. 2166-2173Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: While higher intake of fish and lower consumption of red/processed meats have been suggested to play a protective role in the etiology of several cancers, prospective evidence for hepatocellular carcinoma (HCC) is limited, particularly in Western European populations.

    METHODS: The associations of fish and meats with HCC risk were analyzed in the EPIC cohort. Between 1992 and 2010, 191 incident HCC were identified among 477 206 participants. Baseline diet was assessed using validated dietary questionnaires. A single 24-h diet recall from a cohort subsample was used for calibration. Multivariable proportional hazard regression was utilized to estimate hazard ratios (HR) and 95% confidence intervals (CI). In a nested case-control subset (HCC = 122), HBV/HCV status and liver function biomarkers were measured.

    RESULTS: HCC risk was inversely associated with intake of total fish (per 20 g/day increase, HR = 0.83, 95% CI 0.74-0.95 and HR = 0.80, 95% CI 0.69-0.97 before and after calibration, respectively). This inverse association was also suggested after adjusting for HBV/HCV status and liver function score (per 20-g/day increase, RR = 0.86, 95% CI 0.66-1.11 and RR = 0.74, 95% CI 0.50-1.09, respectively) in a nested case-control subset. Intakes of total meats or subgroups of red/processed meats, and poultry were not associated with HCC risk.

    CONCLUSIONS: In this large European cohort, total fish intake is associated with lower HCC risk.

  • 28. Fedirko, Veronika
    et al.
    Duarte-Salles, Talita
    Bamia, Christina
    Trichopoulou, Antonia
    Aleksandrova, Krasimira
    Trichopoulos, Dimitrios
    Trepo, Elisabeth
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Françoise
    Kvaskoff, Marina
    Kühn, Tilman
    Lukanova, Annie
    Boeing, Heiner
    Buijsse, Brian
    Klinaki, Eleni
    Tsimakidi, Chrysanthi
    Naccarati, Alessio
    Tagliabue, Giovanna
    Panico, Salvatore
    Tumino, Rosario
    Palli, Domenico
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Peters, Petra H
    Lund, Eiliv
    Brustad, Magritt
    Standahl Olsen, Karina
    Weiderpass Vainio, Elisabete
    Zamora, Raul
    Sánchez, María-José
    Ardanaz, Eva
    Amiano, Pilar
    Navarro, Carmen
    Quirós, J Ramón
    Werner, Mårten
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lindkvist, Björn
    Malm, Johan
    Travis, Ruth C
    Khaw, Kay-Tee
    Stepien, Magdalena
    Scalbert, Augustin
    Romieu, Isabelle
    Lagiou, Pagona
    Riboli, Elio
    Jenab, Mazda
    Pre-diagnostic circulating vitamin D levels and risk of hepatocellular carcinoma in European populations: a nested case-control study2014In: Hepatology, ISSN 0270-9139, E-ISSN 1527-3350, Vol. 60, no 4, p. 1222-1230Article in journal (Refereed)
    Abstract [en]

    The association between vitamin D status and hepatocellular carcinoma has not been well investigated, despite experimental evidence supporting an important role of vitamin D in liver pathophysiology. Our objective was to investigate the association between pre-diagnostic circulating 25-hydroxyvitamin D [25(OH)D] serum levels and risk of hepatocellular carcinoma in a prospective, nested case-control study among 520,000 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Each case (n = 138) diagnosed between 1992 and 2010 was matched to one control by age, sex, study center, date and time of blood collection, and fasting status. Serum baseline levels of 25(OH)D were measured by liquid chromatography/tandem mass spectrometry. Multivariable incident rate ratios (IRR) of hepatocellular carcinoma associated with continuous (per 10 nmol/L) or categorical levels (tertiles or a priori-defined categories) of pre-diagnostic 25(OH)D. Higher 25(OH)D levels were associated with a 49% reduction in the risk of hepatocellular carcinoma (highest vs. lowest tertile: multivariable IRR = 0.51, 95% confidence interval, 0.26 to 0.99; Ptrend = 0.04; per 10 nmol/L increase: IRR = 0.80, 95% confidence interval, 0.68-0.94). The finding did not vary substantially by time from enrolment to diagnosis, and did not change after adjustment for biomarkers of pre-existing liver damage, nor chronic infection with hepatitis B or C viruses. The findings were not modified by body size or smoking status. Conclusion: In this prospective study on Western European populations, serum levels of 25(OH)D were inversely associated with risk of hepatocellular carcinoma. Given the rising incidence of this cancer in low-risk developed countries and the strong public health interest surrounding the potentially cancer-protective roles of vitamin D, additional studies in different populations are required. (Hepatology 2014;).

  • 29. Ferrari, Pietro
    et al.
    Rinaldi, Sabina
    Jenab, Mazda
    Lukanova, Annekatrin
    Olsen, Anja
    Tjonneland, Anne
    Overvad, Kim
    Clavel-Chapelon, Francoise
    Fagherazzi, Guy
    Touillaud, Marina
    Kaaks, Rudolf
    von Ruesten, Anne
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Benetou, Vassiliki
    Grioni, Sara
    Panico, Salvatore
    Masala, Giovanna
    Tumino, Rosario
    Polidoro, Silvia
    Bakker, Marije F.
    van Gils, Carla H.
    Ros, Martine M.
    Bueno-de-Mesquita, H. Bas
    Krum-Hansen, Sanda
    Engeset, Dagrun
    Skeie, Guri
    Pilar, Amiano
    Sanchez, Maria-Jose
    Buckland, Genevieve
    Ardanaz, Eva
    Chirlaque, Dolores
    Rodriguez, Laudina
    Travis, Ruth
    Key, Tim
    Khaw, Kay-Tee
    Wareham, Nicholas J.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Slimani, Nadia
    Norat, Teresa
    Aune, Dagfinn
    Riboli, Elio
    Romieu, Isabelle
    Dietary fiber intake and risk of hormonal receptor-defined breast cancer in the European Prospective Investigation into Cancer and Nutrition study2013In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 97, no 2, p. 344-353Article in journal (Refereed)
    Abstract [en]

    Background: Limited scientific evidence has characterized the association between dietary fiber intake and risk of breast cancer (BC) by menopausal status and hormone receptor expression in tumors. ' Objective: We investigated the relation between total dietary fiber and its main food sources (vegetables, fruit, cereals, and legumes) and BC risk by using data from the European Prospective Investigation into Cancer and Nutrition (EPIC). Design: A total of 11,576 invasive BC cases in 334,849 EPIC women mostly aged 35-70 y at baseline were identified over a median follow-up of 11.5 y. Dietary fiber was estimated from country-specific dietary questionnaires. Multivariable Cox proportional hazards regression models were used to quantify the association between dietary variables and BC risk with energy adjustment by using the residual method. Subgroup analyses were performed by menopausal status and estrogen receptor (ER) and progesterone receptor (PR) expression in tumors. Results: BC risk was inversely associated with intakes of total dietary fiber [hazard ratio comparing fifth quintile to first quintile (HRQ5-Q1): 0.95; 95% CI: 0.89, 1.01; P-trend = 0.03] and fiber from vegetables (0.90; 0.84, 0.96; P-trend < 0.01) but not with fiber from fruit, cereals, or legumes. Overall, associations were homogeneous by menopausal status and ER and PR expression in tumors. For vegetable fiber, stronger associations were observed for estrogen receptor-negative and progesterone receptor-negative (HRQ5-Q1: 0.74; 95% CI: 0.59, 0.93; P-trend = 0.01) than for estrogen receptor-positive and progesterone receptor-positive tumors (0.92: 0.81, 1.03; P-trend = 0.05), with P-heterogeneity = 0.09. Conclusion: Diets rich in dietary fiber and, particularly, fiber from vegetables may be associated with a small reduction in risk of BC, independently of menopausal status. 

  • 30.
    Franklin, Oskar
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Billing, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öhlund, Daniel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Berglund, Anette
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Wang, Wanzhong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hellman, Urban
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    CD44 receptors and stromal CD44 ligands as prognostic markers in pancreatic ductal adenocarcinomaManuscript (preprint) (Other academic)
  • 31.
    Franklin, Oskar
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Jonsson, Pär
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Billing, Ola
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundberg, Erik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öhlund, Daniel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Nyström, Hanna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Antti, Henrik
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Plasma micro-RNA alterations appear late in pancreatic cancer2017In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140Article in journal (Refereed)
    Abstract [en]

    Objectives: The aim of this research was to study whether plasma microRNAs (miRNA) can be used for early detection of pancreatic cancer (PC) by analyzing prediagnostic plasma samples collected before a PC diagnosis. Background: PC has a poor prognosis due to late presenting symptoms and early metastasis. Circulating miRNAs are altered in PC at diagnosis but have not been evaluated in a prediagnostic setting. Methods: We first performed an initial screen using a panel of 372 miRNAs in a retrospective case-control cohort that included early-stage PC patients and healthy controls. Significantly altered miRNAs at diagnosis were then measured in an early detection case-control cohort wherein plasma samples in the cases are collected before a PC diagnosis. Carbohydrate antigen 19–9 (Ca 19–9) levels were measured in all samples for comparison. Results: Our initial screen, including 23 stage I-II PC cases and 22 controls, revealed 15 candidate miRNAs that were differentially expressed in plasma samples at PC diagnosis. We combined all 15 miRNAs into a multivariate statistical model, which outperformed Ca 19–9 in receiver-operating characteristics analysis. However, none of the candidate miRNAs, individually or in combination, were significantly altered in prediagnostic plasma samples from 67 future PC patients compared with 132 matched controls. In comparison, Ca 19–9 levels were significantly higher in the cases at <5 years before diagnosis. Conclusion: Plasma miRNAs are altered in PC patients at diagnosis, but the candidate miRNAs found in this study appear late in the course of the disease and cannot be used for early detection of the disease.

  • 32.
    Franklin, Oskar
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öhlund, Daniel
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Lundin, Christina
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Öman, Mikael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Naredi, Peter
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Wang, Wanzhong
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Combining conventional and stroma-derived tumour markers in pancreatic ductal adenocarcinoma2015In: Cancer Biomarkers, ISSN 1574-0153, Vol. 15, no 1, p. 1-10Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: A lack of disease-specific symptoms and good tumour markers makes early detection and diagnosis of pancreatic ductal adenocarcinoma (PDAC) challenging. OBJECTIVE: To analyse the tissue expression and circulating levels of four stroma-derived substances (type IV collagen, endostatin/type XVIII collagen, osteopontin and tenascin C) and four conventional tumour markers (CA 19-9, TPS, CEA and Ca 125) in a PDAC cohort.

    METHODS: Tissue expression of markers in normal pancreas and PDAC tissue was analysed with immunofluorescence. Plasma concentrations of markers were measured before and after surgery. Patients with non-malignant disorders served as controls.

    RESULTS: The conventional and stromal substances were expressed in the cancer cell compartment and the stroma, respectively. Although most patients had increased levels of many markers before surgery, 2/12 (17%) of patients had normal levels of Ca 19-9 at this stage. High preoperative endostatin/type XVIII collagen, and postoperative type IV collagen was associated with short survival. Neither the pre-nor postoperative levels of TPS, Ca 125 or CA 19-9 were associated to survival.

    CONCLUSIONS: PDAC is characterized by an abundant stroma. These initial observations indicate that the stroma can be a source of PDAC tumour markers that are found in different compartments of the cancer, thus reflecting different aspects of tumour biology.

  • 33. Frentzas, Sophia
    et al.
    Simoneau, Eve
    Bridgeman, Victoria L.
    Vermeulen, Peter B.
    Foo, Shane
    Kostaras, Eleftherios
    Nathan, Mark R.
    Wotherspoon, Andrew
    Gao, Zu-Hua
    Shi, Yu
    Van den Eynden, Gert
    Daley, Frances
    Peckitt, Clare
    Tan, Xianming
    Salman, Ayat
    Lazaris, Anthoula
    Gazinska, Patrycja
    Berg, Tracy J.
    Eltahir, Zak
    Ritsma, Laila
    van Rheenen, Jacco
    Khashper, Alla
    Brown, Gina
    Nyström, Hanna
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Van Laere, Steven
    Loyer, Evelyne
    Dirix, Luc
    Cunningham, David
    Metrakos, Peter
    Reynolds, Andrew R.
    Vessel co-option mediates resistance to anti-angiogenic therapy in liver metastases2016In: Nature Medicine, ISSN 1078-8956, E-ISSN 1546-170X, Vol. 22, no 11, p. 1294-1302Article in journal (Refereed)
    Abstract [en]

    The efficacy of angiogenesis inhibitors in cancer is limited by resistance mechanisms that are poorly understood. Notably, instead of through the induction of angiogenesis, tumor vascularization can occur through the nonangiogenic mechanism of vessel co-option. Here we show that vessel co-option is associated with a poor response to the anti-angiogenic agent bevacizumab in patients with colorectal cancer liver metastases. Moreover, we find that vessel co-option is also prevalent in human breast cancer liver metastases, a setting in which results with anti-angiogenic therapy have been disappointing. In preclinical mechanistic studies, we found that cancer cell motility mediated by the actin-related protein 2/3 complex (Arp2/3) is required for vessel co-option in liver metastases in vivo and that, in this setting, combined inhibition of angiogenesis and vessel co-option is more effective than the inhibition of angiogenesis alone. Vessel co-option is therefore a clinically relevant mechanism of resistance to anti-angiogenic therapy and combined inhibition of angiogenesis and vessel co-option might be a warranted therapeutic strategy.

  • 34. Gaudet, Mia M.
    et al.
    Barrdahl, Myrto
    Lindstroem, Sara
    Travis, Ruth C.
    Auer, Paul L.
    Buring, Julie E.
    Chanock, Stephen J.
    Eliassen, A. Heather
    Gapstur, Susan M.
    Giles, Graham G.
    Gunter, Marc
    Haiman, Christopher
    Hunter, David J.
    Joshi, Amit D.
    Kaaks, Rudolf
    Khaw, Kay-Tee
    Lee, I-Min
    Le Marchand, Loic
    Milne, Roger L.
    Peeters, Petra H. M.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Tamimi, Rulla
    Trichopoulou, Antonia
    Weiderpass, Elisabete
    Yang, Xiaohong R.
    Prentice, Ross L.
    Feigelson, Heather Spencer
    Canzian, Federico
    Kraft, Peter
    Interactions between breast cancer susceptibility loci and menopausal hormone therapy in relationship to breast cancer in the Breast and Prostate Cancer Cohort Consortium2016In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 155, no 3, p. 531-540Article in journal (Refereed)
    Abstract [en]

    Current use of menopausal hormone therapy (MHT) has important implications for postmenopausal breast cancer risk, and observed associations might be modified by known breast cancer susceptibility loci. To provide the most comprehensive assessment of interactions of prospectively collected data on MHT and 17 confirmed susceptibility loci with invasive breast cancer risk, a nested case-control design among eight cohorts within the NCI Breast and Prostate Cancer Cohort Consortium was used. Based on data from 13,304 cases and 15,622 controls, multivariable-adjusted logistic regression analyses were used to estimate odds ratios (OR) and 95 % confidence intervals (CI). Effect modification of current and past use was evaluated on the multiplicative scale. P values < 1.5 x 10(-3) were considered statistically significant. The strongest evidence of effect modification was observed for current MHT by 9q31-rs865686. Compared to never users of MHT with the rs865686 GG genotype, the association between current MHT use and breast cancer risk for the TT genotype (OR 1.79, 95 % CI 1.43-2.24; P (interaction) = 1.2 x 10(-4)) was less than expected on the multiplicative scale. There are no biological implications of the sub-multiplicative interaction between MHT and rs865686. Menopausal hormone therapy is unlikely to have a strong interaction with the common genetic variants associated with invasive breast cancer.

  • 35. Ge, Wenzhen
    et al.
    Clendenen, Tess V.
    Afanasyeva, Yelena
    Koenig, Karen L.
    Agnoli, Claudia
    Brinton, Louise A.
    Dorgan, Joanne F.
    Eliassen, A. Heather
    Falk, Roni T.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Hankinson, Susan E.
    Hoffman-Bolton, Judith
    Key, Timothy J.
    Krogh, Vittorio
    Nichols, Hazel B.
    Sandler, Dale P.
    Schoemaker, Minouk J.
    Sluss, Patrick M.
    Sund, Malin
    Department of Surgery, Umeå University Hospital, Umeå, Sweden.
    Swerdlow, Anthony J.
    Visvanathan, Kala
    Liu, Mengling
    Zeleniuch-Jacquotte, Anne
    Circulating anti-Müllerian hormone and breast cancer risk: a study in ten prospective cohorts2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 142, no 11, p. 2215-2226Article in journal (Refereed)
    Abstract [en]

    A strong positive association has been observed between circulating anti‐Müllerian hormone (AMH), a biomarker of ovarian reserve, and breast cancer risk in three prospective studies. Confirming this association is important because of the paucity of biomarkers of breast cancer risk in premenopausal women. We conducted a consortium study including ten prospective cohorts that had collected blood from premenopausal women. A nested case–control design was implemented within each cohort. A total of 2,835 invasive (80%) and in situ (20%) breast cancer cases were individually matched to controls (n = 3,122) on age at blood donation. AMH was measured using a high sensitivity enzyme‐linked immunoabsorbent assay. Conditional logistic regression was applied to the aggregated dataset. There was a statistically significant trend of increasing breast cancer risk with increasing AMH concentration (ptrend across quartiles <0.0001) after adjusting for breast cancer risk factors. The odds ratio (OR) for breast cancer in the top vs. bottom quartile of AMH was 1.60 (95% CI = 1.31–1.94). Though the test for interaction was not statistically significant (pinteraction = 0.15), the trend was statistically significant only for tumors positive for both estrogen receptor (ER) and progesterone receptor (PR): ER+/PR+: ORQ4–Q1 = 1.96, 95% CI = 1.46–2.64, ptrend <0.0001; ER+/PR−: ORQ4–Q1 = 0.82, 95% CI = 0.40–1.68, ptrend = 0.51; ER−/PR+: ORQ4–Q1 = 3.23, 95% CI = 0.48–21.9, ptrend = 0.26; ER−/PR−: ORQ4–Q1 = 1.15, 95% CI = 0.63–2.09, ptrend = 0.60. The association was observed for both pre‐ (ORQ4–Q1= 1.35, 95% CI = 1.05–1.73) and post‐menopausal (ORQ4–Q1 = 1.61, 95% CI = 1.03–2.53) breast cancer (pinteraction = 0.34). In this large consortium study, we confirmed that AMH is associated with breast cancer risk, with a 60% increase in risk for women in the top vs. bottom quartile of AMH.

    What's new? To make informed decisions about screening and prevention, women need tools to accurately assess their breast cancer risk. Young women have few predictive biomarkers to look to; estrogen and progesterone are only weakly predictive before menopause. Anti-Müllerian hormone (AMH), which strongly correlates with age at menopause, may also correlate with breast cancer risk, according to some previous data. Here, the authors test this correlation by conducting nested case-control studies within ten different cohorts. They found that breast cancer risk increased along with increasing AMH concentration, confirming this hormone as a possible biomarker for breast cancer.

  • 36. Georgoudaki, Anna-Maria
    et al.
    Prokopec, Kajsa E.
    Boura, Vanessa F.
    Hellqvist, Eva
    Sohn, Silke
    Ostling, Jeanette
    Dahan, Rony
    Harris, Robert A.
    Rantalainen, Mattias
    Klevebring, Daniel
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Brage, Suzanne Egyhazi
    Fuxe, Jonas
    Rolny, Charlotte
    Li, Fubin
    Ravetch, Jeffrey V.
    Karlsson, Mikael C. I.
    Reprogramming Tumor-Associated Macrophages by Antibody Targeting Inhibits Cancer Progression and Metastasis2016In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 15, no 9, p. 2000-2011Article in journal (Refereed)
    Abstract [en]

    Tumors are composed of multiple cell types besides the tumor cells themselves, including innate immune cells such as macrophages. Tumor-associated macrophages (TAMs) are a heterogeneous population of myeloid cells present in the tumor microenvironment (TME). Here, they contribute to immunosuppression, enabling the establishment and persistence of solid tumors as well as metastatic dissemination. We have found that the pattern recognition scavenger receptor MARCO defines a subtype of suppressive TAMs and is linked to clinical outcome. An anti-MARCO monoclonal antibody was developed, which induces anti-tumor activity in breast and colon carcinoma, as well as in melanoma models through reprogramming-TAM-populations to a pro-inflammatory phenotype and increasing tumor immunogenicity. This anti-tumor activity is dependent on the inhibitory Fc-receptor, Fc gamma RIIB, and also enhances the efficacy of checkpoint therapy. These results demonstrate that immunotherapies using antibodies designed to modify myeloid cells of the TME represent a promising mode of cancer treatment.

  • 37. Grote, V. A.
    et al.
    Rohrmann, S.
    Nieters, A.
    Dossus, L.
    Tjonneland, A.
    Halkjaer, J.
    Overvad, K.
    Fagherazzi, G.
    Boutron-Ruault, M. C.
    Morois, S.
    Teucher, B.
    Becker, S.
    Sluik, D.
    Boeing, H.
    Trichopoulou, A.
    Lagiou, P.
    Trichopoulos, D.
    Palli, D.
    Pala, V.
    Tumino, R.
    Vineis, P.
    Panico, S.
    Rodriguez, L.
    Duell, E. J.
    Molina-Montes, E.
    Dorronsoro, M.
    Huerta, J. M.
    Ardanaz, E.
    Jeurnink, S. M.
    Beulens, J. W. J.
    Peeters, P. H. M.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ye, W.
    Lindkvist, B.
    Johansen, D.
    Khaw, K. T.
    Wareham, N.
    Allen, N.
    Crowe, F.
    Jenab, M.
    Romieu, I.
    Michaud, D. S.
    Riboli, E.
    Romaguera, D.
    Bueno-de-Mesquita, H. B.
    Kaaks, R.
    Diabetes mellitus, glycated haemoglobin and C-peptide levels in relation to pancreatic cancer risk: a study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2011In: Diabetologia, ISSN 0012-186X, E-ISSN 1432-0428, Vol. 54, no 12, p. 3037-3046Article in journal (Refereed)
    Abstract [en]

    Aims/hypothesis: There has been long-standing debate about whether diabetes is a causal risk factor for pancreatic cancer or a consequence of tumour development. Prospective epidemiological studies have shown variable relationships between pancreatic cancer risk and blood markers of glucose and insulin metabolism, overall and as a function of lag times between marker measurements (blood donation) and date of tumour diagnosis.

    Methods: Pre-diagnostic levels of HbA(1c) and C-peptide were measured for 466 participants with pancreatic cancer and 466 individually matched controls within the European Prospective Investigation into Cancer and Nutrition. Conditional logistic regression models were used to estimate ORs for pancreatic cancer.

    Results: Pancreatic cancer risk gradually increased with increasing pre-diagnostic HbA(1c) levels up to an OR of 2.42 (95% CI 1.33, 4.39 highest [>= 6.5%, 48 mmol/mol] vs lowest [<= 5.4%, 36 mmol/mol] category), even for individuals with HbA(1c) levels within the non-diabetic range. C-peptide levels showed no significant relationship with pancreatic cancer risk, irrespective of fasting status. Analyses showed no clear trends towards increasing hyperglycaemia (as marked by HbA(1c) levels) or reduced pancreatic beta cell responsiveness (as marked by C-peptide levels) with decreasing time intervals from blood donation to cancer diagnosis.

    Conclusions/interpretation: Our data on HbA(1c) show that individuals who develop exocrine pancreatic cancer tend to have moderate increases in HbA(1c) levels, relatively independently of obesity and insulin resistance-the classic and major risk factors for type 2 diabetes. While there is no strong difference by lag time, more data are needed on this in order to reach a firm conclusion.

  • 38. Grote, VA
    et al.
    Kaaks, R
    Nieters, A
    Tjonneland, A
    Halkjaer, J
    Overvad, K
    Nielsen, MR Skjelbo
    Boutron-Ruault, MC
    Clavel-Chapelon, F
    Racine, A
    Teucher, B
    Becker, S
    Pischon, T
    Boeing, H
    Trichopoulou, A
    Cassapa, C
    Stratigakou, V
    Palli, D
    Krogh, V
    Tumino, R
    Vineis, P
    Panico, S
    Rodriguez, L
    Duell, EJ
    Sanchez, M-J
    Dorronsoro, M
    Navarro, C
    Gurrea, AB
    Siersema, PD
    Peeters, PHM
    Ye, W
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Lindkvist, B
    Johansen, D
    Khaw, K-T
    Wareham, N
    Allen, NE
    Travis, RC
    Fedirko, V
    Jenab, M
    Michaud, DS
    Chuang, S-C
    Romaguera, D
    Bueno-de-Mesquita, HB
    Rohrmann, S
    Inflammation marker and risk of pancreatic cancer: a nested case-control study within the EPIC cohort2012In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 106, no 11, p. 1866-1874Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Established risk factors for pancreatic cancer include smoking, long-standing diabetes, high body fatness, and chronic pancreatitis, all of which can be characterised by aspects of inflammatory processes. However, prospective studies investigating the relation between inflammatory markers and pancreatic cancer risk are scarce.

    METHODS: We conducted a nested case-control study within the European Prospective Investigation into Cancer and Nutrition, measuring prediagnostic blood levels of C-reactive protein (CRP), interleukin-6 (IL-6), and soluble receptors of tumour necrosis factor-a (sTNF-R1, R2) in 455 pancreatic cancer cases and 455 matched controls. Odds ratios (ORs) were estimated using conditional logistic regression models.

    RESULTS: None of the inflammatory markers were significantly associated with risk of pancreatic cancer overall, although a borderline significant association was observed for higher circulating sTNF-R2 (crude OR = 1.52 (95% confidence interval (CI) 0.97-2.39), highest vs lowest quartile). In women, however, higher sTNF-R1 levels were significantly associated with risk of pancreatic cancer (crude OR = 1.97 (95% CI 1.02-3.79)). For sTNF-R2, risk associations seemed to be stronger for diabetic individuals and those with a higher BMI.

    CONCLUSION: Prospectively, CRP and IL-6 do not seem to have a role in our study with respect to risk of pancreatic cancer, whereas sTNF-R1 seemed to be a risk factor in women and sTNF-R2 might be a mediator in the risk relationship between overweight and diabetes with pancreatic cancer. Further large prospective studies are needed to clarify the role of proinflammatory proteins and cytokines in the pathogenesis of exocrine pancreatic cancer. British Journal of Cancer (2012) 106, 1866-1874. doi:10.1038/bjc.2012.172 www.bjcancer.com Published online 26 April 2012 (C) 2012 Cancer Research UK

  • 39. Grote, Verena A.
    et al.
    Nieters, Alexandra
    Kaaks, Rudolf
    Tjonneland, Anne
    Roswall, Nina
    Overvad, Kim
    Nielsen, Michael R. Skjelbo
    Clavel-Chapelon, Francoise
    Boutron-Ruault, Marie Christine
    Racine, Antoine
    Teucher, Birgit
    Lukanova, Annekatrin
    Boeing, Heiner
    Drogan, Dagmar
    Trichopoulou, Antonia
    Trichopoulos, Dimitrios
    Lagiou, Pagona
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Argueelles Suarez, Marcial Vicente
    Duell, Eric J.
    Sanchez, Maria-Jose
    Dorronsoro, Miren
    Huerta Castano, Jose Maria
    Barricarte, Aurelio
    Jeurnink, Suzanne M.
    Peeters, Petra H. M.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ye, Weimin
    Regner, Sara
    Lindkvist, Bjorn
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E.
    Crowe, Francesca L.
    Fedirko, Veronika
    Jenab, Mazda
    Romaguera, Dora
    Siddiq, Afshan
    Bueno-de-Mesquita, H. Bas
    Rohrmann, Sabine
    The associations of advanced Glycation end products and its soluble receptor with Pancreatic Cancer risk: A Case-Control Study within the Prospective EPIC Cohort2012In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 21, no 4, p. 619-628Article in journal (Refereed)
    Abstract [en]

    Background: Advanced glycation end products (AGE) and their receptors (RAGE) have been implicated in cancer development through their proinflammatory capabilities. However, prospective data on their association with cancer of specific sites, including pancreatic cancer, are limited. Methods: Prediagnostic blood levels of the AGE product Ne-(carboxymethyl) lysine (CML) and the endogenous secreted receptor for AGE (esRAGE) were measured using ELISA in 454 patients with exocrine pancreatic cancer and individually matched controls within the European Prospective Investigation into Cancer and Nutrition (EPIC). Pancreatic cancer risk was estimated by calculating ORs with corresponding 95% confidence intervals (CI). Results: Elevated CML levels tended to be associated with a reduction in pancreatic cancer risk [OR = 0.57 (95% CI, 0.32-1.01) comparing highest with lowest quintile), whereas no association was observed for esRAGE (OR = 0.98; 95% CI, 0.62-1.54). Adjustments for body mass index and smoking attenuated the inverse associations of CML with pancreatic cancer risk (OR = 0.78; 95% CI, 0.41-1.49). There was an inverse association between esRAGE and risk of pancreatic cancer for cases that were diagnosed within the first 2 years of follow-up [OR = 0.46 (95% CI, 0.22-0.96) for a doubling in concentration], whereas there was no association among those with a longer follow-up (OR = 1.11; 95% CI, 0.88-1.39; P-interaction = 0.002). Conclusions and Impact: Our results do not provide evidence for an association of higher CML or lower esRAGE levels with risk of pancreatic cancer. The role of AGE/RAGE in pancreatic cancer would benefit from further investigations. Cancer Epidemiol Biomarkers Prev; 21(4); 619-28. (C) 2012 AACR.

  • 40. Grote, Verena A.
    et al.
    Rohrmann, Sabine
    Dossus, Laure
    Nieters, Alexandra
    Halkjaer, Jytte
    Tjonneland, Anne
    Overvad, Kim
    Stegger, Jakob
    Chabbert-Buffet, Nathalie
    Boutron-Ruault, Marie-Christine
    Clavel-Chapelon, Francoise
    Teucher, Birgit
    Becker, Susen
    Montonen, Jukka
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Argueelles, Marcial
    Duell, Eric J.
    Molina-Montes, Esther
    Larranaga, Nerea
    Chirlaque, Maria-Dolores
    Gurrea, Aurelio Barricarte
    Jeurnink, Suzanne M.
    Peeters, Petra H. M.
    Ye, Weimin
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Lindkvist, Bjoern
    Johansen, Dorthe
    Khaw, Kay-Tee
    Wareham, Nick
    Crowe, Francesca L.
    Romieu, Isabelle
    Rinaldi, Sabina
    Jenab, Mazda
    Romaguera, Dora
    Michaud, Dominique S.
    Riboli, Elio
    Bueno-de-Mesquita, H. Bas
    Kaaks, Rudolf
    The association of circulating adiponectin levels with pancreatic cancer risk: A study within the prospective EPIC cohort2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 130, no 10, p. 2428-2437Article in journal (Refereed)
    Abstract [en]

    Excess body weight and type 2 diabetes mellitus, risk factors of pancreatic cancer, are characterized by decreased levels of adiponectin. In addition to anti-inflammatory and anti-proliferative actions, adiponectin has an important role in regulating glucose metabolism, i.e., decreasing circulating blood glucose levels. Prospectively, hyperglycemia has been associated with risk of pancreatic cancer. The aim of this study was to investigate the association of pre-diagnostic adiponectin levels with pancreatic cancer risk. We conducted a casecontrol study nested within European Prospective Investigation into Cancer and Nutrition. Blood samples of 452 pancreatic cancer cases and 452 individually matched controls were analyzed by immunoassays. Multivariate conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Overall, adiponectin showed no association with pancreas cancer risk; however, among never smokers, higher circulating levels of adiponectin were associated with a reduction in pancreatic cancer risk (OR = 0.44 [95% CI 0.230.82] for highest vs. lowest quartile), whereas among current smokers there was no significant association (OR = 1.59 [95% CI 0.673.76] for highest vs. lowest quartile; p-trend = 0.530; p-interaction = 0.309). In our study, lower adiponectin concentrations may be associated with the development of pancreatic cancer among never smokers, whereas the only other prospective study being conducted so far showed a decrease in risk among male smokers. Therefore, further studies are needed to clarify the role of adiponectin in pancreatic cancer development.

  • 41. Jacobs, Eric J
    et al.
    Chanock, Stephen J
    Fuchs, Charles S
    Lacroix, Andrea
    McWilliams, Robert R
    Steplowski, Emily
    Stolzenberg-Solomon, Rachael Z
    Arslan, Alan A
    Bueno-de-Mesquita, H Bas
    Gross, Myron
    Helzlsouer, Kathy
    Petersen, Gloria
    Zheng, Wei
    Agalliu, Ilir
    Allen, Naomi E
    Amundadottir, Laufey
    Boutron-Ruault, Marie-Christine
    Buring, Julie E
    Canzian, Federico
    Clipp, Sandra
    Dorronsoro, Miren
    Gaziano, J Michael
    Giovannucci, Edward L
    Hankinson, Susan E
    Hartge, Patricia
    Hoover, Robert N
    Hunter, David J
    Jacobs, Kevin B
    Jenab, Mazda
    Kraft, Peter
    Kooperberg, Charles
    Lynch, Shannon M
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Mendelsohn, Julie B
    Mouw, Tracy
    Newton, Christina C
    Overvad, Kim
    Palli, Domenico
    Peeters, Petra H M
    Rajkovic, Aleksandar
    Shu, Xiao-Ou
    Thomas, Gilles
    Tobias, Geoffrey S
    Trichopoulos, Dimitrios
    Virtamo, Jarmo
    Wactawski-Wende, Jean
    Wolpin, Brian M
    Yu, Kai
    Zeleniuch-Jacquotte, Anne
    Family history of cancer and risk of pancreatic cancer: A pooled analysis from the Pancreatic Cancer Cohort Consortium (PanScan).2010In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215Article in journal (Refereed)
    Abstract [en]

    A family history of pancreatic cancer has consistently been associated with increased risk of pancreatic cancer. However, uncertainty remains about the strength of this association. Results from previous studies suggest a family history of select cancers (i.e., ovarian, breast and colorectal) could also be associated, although not as strongly, with increased risk of pancreatic cancer. We examined the association between a family history of 5 types of cancer (pancreas, prostate, ovarian, breast and colorectal) and risk of pancreatic cancer using data from a collaborative nested case-control study conducted by the Pancreatic Cancer Cohort Consortium. Cases and controls were from cohort studies from the United States, Europe and China, and a case-control study from the Mayo Clinic. Analyses of family history of pancreatic cancer included 1,183 cases and 1,205 controls. A family history of pancreatic cancer in a parent, sibling or child was associated with increased risk of pancreatic cancer [multivariate-adjusted odds ratios (ORs) = 1.76, 95% confidence interval (CI) = 1.19-2.61]. A family history of prostate cancer was also associated with increased risk (OR = 1.45, 95% CI = 1.12-1.89). There were no statistically significant associations with a family history of ovarian cancer (OR = 0.82, 95% CI = 0.52-1.31), breast cancer (OR = 1.21, 95% CI = 0.97-1.51) or colorectal cancer (OR = 1.17, 95% CI = 0.93-1.47). Our results confirm a moderate sized association between a family history of pancreatic cancer and risk of pancreatic cancer and also provide evidence for an association with a family history of prostate cancer worth further study.

  • 42. Jeurnink, Suzanne M.
    et al.
    Ros, Martine M.
    Leenders, Max
    van Duijnhoven, Franzel J. B.
    Siersema, Peter D.
    Jansen, Eugene H. J. M.
    van Gils, Carla H.
    Bakker, Marije F.
    Overvad, Kim
    Roswall, Nina
    Tjonneland, Anne
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Cadeau, Claire
    Grote, Verena
    Kaaks, Rudolf
    Aleksandrova, Krasimira
    Boeing, Heiner
    Trichopoulou, Antonia
    Benetou, Vasiliki
    Valanou, Elisavet
    Palli, Domenico
    Krogh, Vittorio
    Vineis, Paolo
    Tumino, Rosario
    Mattiello, Amalia
    Weiderpass, Elisabete
    Skeie, Guri
    Huerta Castano, Jose Maria
    Duell, Eric J.
    Barricarte, Aurelio
    Molina-Montes, Esther
    Argueelles, Marcial
    Dorronsoro, Mire
    Johansen, Dorthe
    Lindkvist, Bjorn
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Crowe, Francesca L.
    Khaw, Kay-Tee
    Jenab, Mazda
    Fedirko, Veronika
    Riboli, E.
    Bueno-de-Mesquita, H. B(as)
    Plasma carotenoids, vitamin C, retinol and tocopherols levels and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition: A nested case-control study Plasma micronutrients and pancreatic cancer risk2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 6, p. E665-E676Article in journal (Refereed)
    Abstract [en]

    Evidence of a protective effect of several antioxidants and other nutrients on pancreatic cancer risk is inconsistent. The aim of this study was to investigate the association for prediagnostic plasma levels of carotenoids, vitamin C, retinol and tocopherols with risk of pancreatic cancer in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). 446 incident exocrine pancreatic cancer cases were matched to 446 controls by age at blood collection, study center, sex, date and time of blood collection, fasting status and hormone use. Plasma carotenoids (- and -carotene, lycopene, -cryptoxanthin, canthaxanthin, zeaxanthin and lutein), - and -tocopherol and retinol were measured by reverse phase high-performance liquid chromatography and plasma vitamin C by a colorimetric assay. Incidence rate ratios (IRRs) with 95% confidence intervals (95%CIs) for pancreatic cancer risk were estimated using a conditional logistic regression analysis, adjusted for smoking status, smoking duration and intensity, waist circumference, cotinine levels and diabetes status. Inverse associations with pancreatic cancer risk were found for plasma -carotene (IRR highest vs. lowest quartile 0.52, 95%CI 0.31-0.88, p for trend=0.02), zeaxanthin (IRR highest vs. lowest quartile 0.53, 95%CI 0.30-0.94, p for trend=0.06) and -tocopherol (IRR highest vs. lowest quartile 0.62, 95%CI 0.39-0.99, p for trend=0.08. For - and -carotene, lutein, sum of carotenoids and -tocopherol, heterogeneity between geographical regions was observed. In conclusion, our results show that higher plasma concentrations of -carotene, zeaxanthin and -tocopherol may be inversely associated with risk of pancreatic cancer, but further studies are warranted. What's new? Fruits and vegetables may play a role in the prevention of pancreatic cancer, but associations between the antioxidants those foods contain and disease risk remain unclear. In this study, pancreatic cancer risk was inversely associated with increased prediagnostic plasma concentrations of the antioxidants -carotene, zeaxanthin, and -tocopherol. Geographic variations were also detected. In Northern European countries, inverse associations with risk were found for blood levels of several carotenoids, whereas the association was strongest for -tocopherol in Southern European countries. The role of carotenoids and vitamins should be considered in subsequent investigations of the etiology of pancreatic cancer.

  • 43. Johansson, J.
    et al.
    Berg, T.
    Kurzejamska, E.
    Pang, M-F
    Tabor, V.
    Jansson, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Roswall, P.
    Pietras, K.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Religa, P.
    Fuxe, J.
    MiR-155-mediated loss of C/EBP beta shifts the TGF-beta response from growth inhibition to epithelial-mesenchymal transition, invasion and metastasis in breast cancer2013In: Oncogene, ISSN 0950-9232, E-ISSN 1476-5594, Vol. 32, no 50, p. 5614-5624Article in journal (Refereed)
    Abstract [en]

    During breast cancer progression, transforming growth factor-beta (TGF-beta) switches from acting as a growth inhibitor to become a major promoter of epithelial-mesenchymal transition (EMT), invasion and metastasis. However, the mechanisms involved in this switch are not clear. We found that loss of CCAAT-enhancer binding protein beta (C/EBP beta), a differentiation factor for the mammary epithelium, was associated with signs of EMT in triple-negative human breast cancer, and in invasive areas of mammary tumors in MMTV-PyMT mice. Using an established model of TGF-beta-induced EMT in mouse mammary gland epithelial cells, we discovered that C/EBP beta was repressed during EMT by miR-155, an oncomiR in breast cancer. Depletion of C/EBP beta potentiated the TGF-beta response towards EMT, and contributed to evasion of the growth inhibitory response to TGF-beta. Furthermore, loss of C/EBP beta enhanced invasion and metastatic dissemination of the mouse mammary tumor cells to the lungs after subcutaneous injection into mice. The mechanism by which loss of C/EBP beta promoted the TGF-beta response towards EMT, invasion and metastasis, was traced to a previously uncharacterized role of C/EBP beta as a transcriptional activator of genes encoding the epithelial junction proteins E-cadherin and coxsackie virus and adenovirus receptor. The results identify miR-155-mediated loss of C/EBP beta as a mechanism, which promotes breast cancer progression by shifting the TGF-beta response from growth inhibition to EMT, invasion and metastasis.

  • 44. Joshi, Amit D.
    et al.
    Lindström, Sara
    Hüsing, Anika
    Barrdahl, Myrto
    VanderWeele, Tyler J.
    Campa, Daniele
    Canzian, Federico
    Gaudet, Mia M.
    Figueroa, Jonine D.
    Baglietto, Laura
    Berg, Christine D.
    Buring, Julie E.
    Chanock, Stephen J.
    Chirlaque, María-Dolores
    Diver, W. Ryan
    Dossus, Laure
    Giles, Graham G.
    Haiman, Christopher A.
    Hankinson, Susan E.
    Henderson, Brian E.
    Hoover, Robert N.
    Hunter, David J.
    Isaacs, Claudine
    Kaaks, Rudolf
    Kolonel, Laurence N.
    Krogh, Vittorio
    Le Marchand, Loic
    Lee, I-Min
    Lund, Eiliv
    McCarty, Catherine A.
    Overvad, Kim
    Peeters, Petra H.
    Riboli, Elio
    Schumacher, Fredrick
    Severi, Gianluca
    Stram, Daniel O.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Thun, Michael J.
    Travis, Ruth C.
    Trichopoulos, Dimitrios
    Willett, Walter C.
    Zhang, Shumin
    Ziegler, Regina G.
    Kraft, Peter
    Additive interactions between susceptibility single-nucleotide polymorphisms identified in genome-wide association studies and breast cancer risk factors in the Breast and Prostate Cancer Cohort Consortium2014In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 180, no 10, p. 1018-1027Article in journal (Refereed)
    Abstract [en]

    Additive interactions can have public health and etiological implications but are infrequently reported. We assessed departures from additivity on the absolute risk scale between 9 established breast cancer risk factors and 23 susceptibility single-nucleotide polymorphisms (SNPs) identified from genome-wide association studies among 10,146 non-Hispanic white breast cancer cases and 12,760 controls within the National Cancer Institute's Breast and Prostate Cancer Cohort Consortium. We estimated the relative excess risk due to interaction and its 95% confidence interval for each pairwise combination of SNPs and nongenetic risk factors using age- and cohort-adjusted logistic regression models. After correction for multiple comparisons, we identified a statistically significant relative excess risk due to interaction (uncorrected P = 4.51 x 10(-5)) between a SNP in the DNA repair protein RAD51 homolog 2 gene (RAD51L1; rs10483813) and body mass index (weight (kg)/height (m)(2)). We also compared additive and multiplicative polygenic risk prediction models using per-allele odds ratio estimates from previous studies for breast-cancer susceptibility SNPs and observed that the multiplicative model had a substantially better goodness of fit than the additive model.

  • 45. Kaaks, Rudolf
    et al.
    Johnson, Theron
    Tikk, Kaja
    Sookthai, Disorn
    Tjønneland, Anne
    Roswall, Nina
    Overvad, Kim
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Dossus, Laure
    Rinaldi, Sabina
    Romieu, Isabelle
    Boeing, Heiner
    Schütze, Madlen
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Grioni, Sara
    Tumino, Rosario
    Sacerdote, Carlotta
    Panico, Salvatore
    Buckland, Genevieve
    Argüelles, Marcial
    Sánchez, María-José
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Bueno-de-Mesquita, H Bas
    van Gils, Carla H
    Peeters, Petra H
    Andersson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Weiderpass, Elisabete
    Gram, Inger Torhild
    Lund, Eiliv
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J
    Travis, Ruth C
    Merritt, Melissa A
    Gunter, Marc J
    Riboli, Elio
    Lukanova, Annekatrin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Insulin-like growth factor I and risk of breast cancer by age and hormone receptor status: A prospective study within the EPIC cohort2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 11, p. 2683-2690Article in journal (Refereed)
    Abstract [en]

    Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case–control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR)Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01–1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04–1.33] per 1-standard deviation (SD) increase in IGF-I, ptrend = 0.01) and among women who were diagnosed with breast cancer at 50 years or older (ORQ3-Q1 = 1.38 [95% CI 1.01–1.89]; OR = 1.19 [95% CI 1.04–1.36] per 1-SD increase in IGF-I, ptrend = 0.01) but not with receptor-positive disease diagnosed at an earlier age. No statistically significant associations were observed for ER− breast tumors overall and by age at diagnosis. Tests for heterogeneity by receptor status of the tumor were not statistically significant, except for women diagnosed with breast cancer at 50 years or older (phet = 0.03 for ER+/PR+ vs. ER−/PR− disease). Our data add to a global body of evidence indicating that higher circulating IGF-I levels may increase risk specifically of receptor-positive, but not receptor-negative, breast cancer diagnosed at 50 years or older.

  • 46. Kaaks, Rudolf
    et al.
    Tikk, Kaja
    Sookthai, Disorn
    Schock, Helena
    Johnson, Theron
    Tjonneland, Anne
    Olsen, Anja
    Overvad, Kim
    Clavel-Chapelon, Francoise
    Dossus, Laure
    Baglietto, Laura
    Rinaldi, Sabina
    Chajes, Veronique
    Romieu, Isabelle
    Boeing, Heiner
    Schuetze, Madlen
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Palli, Domenico
    Sieri, Sabina
    Tumino, Rosario
    Ricceri, Fulvio
    Mattiello, Amalia
    Buckland, Genevieve
    Ramon Quiros, Jose
    Sanchez, Maria-Jose
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Barricarte, Aurelio
    Bas Bueno-de-Mesquita, H.
    van Gils, Carla H.
    Peeters, Petra H.
    Andersson, Anne
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Weiderpass, Elisabete
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J.
    Travis, Ruth C.
    Merritt, Melissa A.
    Gunter, Marc J.
    Riboli, Elio
    Lukanova-McGregor, Annekatrin
    Premenopausal serum sex hormone levels in relation to breast cancer risk, overall and by hormone receptor status-Results from the EPIC cohort2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 8, p. 1947-1957Article in journal (Refereed)
    Abstract [en]

    Results from prospective studies on premenopausal serum hormone levels in relation to breast cancer risk have been inconclusive, especially with regard to tumor subtypes. Using a case-control study nested within the prospective European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (801 breast cancer cases and 1,132 matched control subjects), we analyzed the relationships of prediagnostic serum estradiol, free estradiol, progesterone, testosterone, free testosterone and sex hormone-binding globulin (SHBG) levels with the risk of breast cancer by estrogen and progesterone receptor-positive and -negative breast tumors and by age at diagnoses. Higher prediagnostic serum levels of testosterone and free testosterone were associated with an increased overall risk of breast cancer [ORQ4-Q1=1.56 (95% CI 1.15-2.13), p(trend)=0.02 for testosterone and ORQ4-Q1=1.33 (95% CI 0.99-1.79), p(trend)=0.04 for free testosterone], but no significant risk association was observed for estradiol, free estradiol, progesterone and SHBG. Tests for heterogeneity between receptor-positive and -negative tumors were not significant. When analysis were stratified by age at tumor diagnosis, the odds ratios observed for estradiol were stronger and borderline significant for breast cancer diagnosed at age less than 50 [ORQ4-Q1=1.32 (95% CI 0.87-2.01), p(trend)=0.05] compared to breast cancer diagnosed at age 50 or above [ORQ4-Q1=0.94 (95% CI 0.60-1.47), p(trend)=0.34, p(het)=0.04]. In conclusion, our data indicate that higher premenopausal circulating testosterone levels are associated with an increased risk of developing breast cancer, but do not show a significant association of estradiol or progesterone with breast cancer risk, overall, by menstrual cycle phase or by tumor receptor status, although a possible risk increase with higher estradiol levels for tumors diagnosed before age 50 was seen.

  • 47. Karakatsanis, A.
    et al.
    Oloffson, H.
    Bergkvist, L. A.
    Abdsaleh, S.
    Sund, Malin
    Warnberg, F.
    How to avoid unnecessary sentinel node biopsy in patients with ductal cancer in situ2015In: Breast, ISSN 0960-9776, E-ISSN 1532-3080, Vol. 24 1, p. S133-S134Article in journal (Other academic)
  • 48. Klein, Alison P.
    et al.
    Wolpin, Brian M.
    Risch, Harvey A.
    Stolzenberg-Solomon, Rachael Z.
    Mocci, Evelina
    Zhang, Mingfeng
    Canzian, Federico
    Childs, Erica J.
    Hoskins, Jason W.
    Jermusyk, Ashley
    Zhong, Jun
    Chen, Fei
    Albanes, Demetrius
    Andreotti, Gabriella
    Arslan, Alan A.
    Babic, Ana
    Bamlet, William R.
    Beane-Freeman, Laura
    Berndt, Sonja I.
    Blackford, Amanda
    Borges, Michael
    Borgida, Ayelet
    Bracci, Paige M.
    Brais, Lauren
    Brennan, Paul
    Brenner, Hermann
    Bueno-de-Mesquita, Bas
    Buring, Julie
    Campa, Daniele
    Capurso, Gabriele
    Cavestro, Giulia Martina
    Chaffee, Kari G.
    Chung, Charles C.
    Cleary, Sean
    Cotterchio, Michelle
    Dijk, Frederike
    Duell, Eric J.
    Foretova, Lenka
    Fuchs, Charles
    Funel, Niccola
    Gallinger, Steven
    Gaziano, J. Michael M.
    Gazouli, Maria
    Giles, Graham G.
    Giovannucci, Edward
    Goggins, Michael
    Goodman, Gary E.
    Goodman, Phyllis J.
    Hackert, Thilo
    Haiman, Christopher
    Hartge, Patricia
    Hasan, Manal
    Hegyi, Peter
    Helzlsouer, Kathy J.
    Herman, Joseph
    Holcatova, Ivana
    Holly, Elizabeth A.
    Hoover, Robert
    Hung, Rayjean J.
    Jacobs, Eric J.
    Jamroziak, Krzysztof
    Janout, Vladimir
    Kaaks, Rudolf
    Khaw, Kay-Tee
    Klein, Eric A.
    Kogevinas, Manolis
    Kooperberg, Charles
    Kulke, Matthew H.
    Kupcinskas, Juozas
    Kurtz, Robert J.
    Laheru, Daniel
    Landi, Stefano
    Lawlor, Rita T.
    Lee, I. -Min
    LeMarchand, Loic
    Lu, Lingeng
    Malats, Nuria
    Mambrini, Andrea
    Mannisto, Satu
    Milne, Roger L.
    Mohelnikova-Duchonova, Beatrice
    Neale, Rachel E.
    Neoptolemos, John P.
    Oberg, Ann L.
    Olson, Sara H.
    Orlow, Irene
    Pasquali, Claudio
    Patel, Alpa V.
    Peters, Ulrike
    Pezzilli, Raffaele
    Porta, Miquel
    Real, Francisco X.
    Rothman, Nathaniel
    Scelo, Ghislaine
    Sesso, Howard D.
    Severi, Gianluca
    Shu, Xiao-Ou
    Silverman, Debra
    Smith, Jill P.
    Soucek, Pavel
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Talar-Wojnarowska, Renata
    Tavano, Francesca
    Thornquist, Mark D.
    Tobias, Geoffrey S.
    Van Den Eeden, Stephen K.
    Vashist, Yogesh
    Visvanathan, Kala
    Vodicka, Pavel
    Wactawski-Wende, Jean
    Wang, Zhaoming
    Wentzensen, Nicolas
    White, Emily
    Yu, Herbert
    Yu, Kai
    Zeleniuch-Jacquotte, Anne
    Zheng, Wei
    Kraft, Peter
    Li, Donghui
    Chanock, Stephen
    Obazee, Ofure
    Petersen, Gloria M.
    Amundadottir, Laufey T.
    Genome-wide meta-analysis identifies five new susceptibility loci for pancreatic cancer2018In: Nature Communications, ISSN 2041-1723, E-ISSN 2041-1723, Vol. 9, article id 556Article in journal (Refereed)
    Abstract [en]

    In 2020, 146,063 deaths due to pancreatic cancer are estimated to occur in Europe and the United States combined. To identify common susceptibility alleles, we performed the largest pancreatic cancer GWAS to date, including 9040 patients and 12,496 controls of European ancestry from the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4). Here, we find significant evidence of a novel association at rs78417682 (7p12/TNS3, P = 4.35 x 10(-8)). Replication of 10 promising signals in up to 2737 patients and 4752 controls from the PANcreatic Disease ReseArch (PAN-DoRA) consortium yields new genome-wide significant loci: rs13303010 at 1p36.33 (NOC2L, P = 8.36 x 10(-14)), rs2941471 at 8q21.11 (HNF4G, P = 6.60 x 10(-10)), rs4795218 at 17q12 (HNF1B, P = 1.32 x 10(-8)), and rs1517037 at 18q21.32 (GRP, P = 3.28 x 10(-8)). rs78417682 is not statistically significantly associated with pancreatic cancer in PANDoRA. Expression quantitative trait locus analysis in three independent pancreatic data sets provides molecular support of NOC2L as a pancreatic cancer susceptibility gene.

  • 49. Krug, S.
    et al.
    Beyer, G.
    Javed, M. A.
    Le, N.
    Vinci, A.
    Morgan, R. D.
    Hubner, R.
    Valle, J. W.
    Wong, H.
    Chowdhury, S.
    Ma, Y. Ting
    Palmer, D.
    Maisonneuve, P.
    Neesse, A.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Schober, M.
    Intensified chemotherapy for metastatic pancreatic cancer: interim analysis of a large retrospective pan-European database and real life evaluation2016In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 27Article in journal (Refereed)
  • 50. Kyrø, Cecilie
    et al.
    Zamora-Ros, Raul
    Scalbert, Augustin
    Tjønneland, Anne
    Dossus, Laure
    Johansen, Christoffer
    Bidstrup, Pernille Envold
    Weiderpass, Elisabete
    Christensen, Jane
    Ward, Heather
    Aune, Dagfinn
    Riboli, Elio
    His, Mathilde
    Clavel-Chapelon, Françoise
    Baglietto, Laura
    Katzke, Verena
    Kühn, Tilman
    Boeing, Heiner
    Floegel, Anna
    Overvad, Kim
    Lasheras, Cristina
    Travier, Noémie
    Sánchez, Maria-José
    Amiano, Pilar
    Chirlaque, Maria-Dolores
    Ardanaz, Eva
    Khaw, Kay-Tee
    Wareham, Nick
    Perez-Cornago, Aurora
    Trichopoulou, Antonia
    Lagiou, Pagona
    Vasilopoulou, Effie
    Masala, Giovanna
    Grioni, Sara
    Berrino, Franco
    Tumino, Rosario
    Sacerdote, Carlotta
    Mattiello, Amalia
    Bueno-de-Mesquita, H B(as)
    Peeters, Petra H
    van Gils, Carla
    Borgquist, Signe
    Butt, Salma
    Zeleniuch-Jacquotte, Anne
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Hjartåker, Anette
    Skeie, Guri
    Olsen, Anja
    Romieu, Isabelle
    Pre-diagnostic polyphenol intake and breast cancer survival: the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort2015In: Breast Cancer Research and Treatment, ISSN 0167-6806, E-ISSN 1573-7217, Vol. 154, no 2, p. 389-401Article in journal (Refereed)
    Abstract [en]

    The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status.

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