umu.sePublications
Change search
Refine search result
123 1 - 50 of 107
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Rows per page
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sort
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
  • Standard (Relevance)
  • Author A-Ö
  • Author Ö-A
  • Title A-Ö
  • Title Ö-A
  • Publication type A-Ö
  • Publication type Ö-A
  • Issued (Oldest first)
  • Issued (Newest first)
  • Created (Oldest first)
  • Created (Newest first)
  • Last updated (Oldest first)
  • Last updated (Newest first)
Select
The maximal number of hits you can export is 250. When you want to export more records please use the 'Create feeds' function.
  • 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, 178-187 p.Article 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. 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, 1244-1250 p.Article 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.

  • 3. 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, 1498-1508 p.Article 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.

  • 4. 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, 858-871 p.Article 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.

  • 5. 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, 454-464 p.Article 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.

  • 6. 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, 1899-1908 p.Article 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.

  • 7. 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, 5260-5270 p.Article 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.

  • 8. 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, 2837-2845 p.Article 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.

  • 9. 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 Study.2013In: Clinical Gastroenterology and Hepatology, ISSN 1542-3565, E-ISSN 1542-7714, Vol. 11, no 1, 1486-1492 p.Article 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.

  • 10. 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, 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.

  • 11. 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, e85955- p.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''.

  • 12. 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, 761-767 p.Article 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.

  • 13. 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, 2447-2454 p.Article 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.

  • 14. 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, 1808-1816 p.Article 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.

  • 15. 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, 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.

  • 16. 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, 92-101 p.Article 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.

  • 17. 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, 2164-2175 p.Article 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.

  • 18. 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 Public Health and Clinical Medicine.
    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, 613-621 p.Article 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.

  • 19. 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, 2887-2899 p.Article 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.

  • 20. 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, 2065-2076 p.Article 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.

  • 21. 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, 543-553 p.Article 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.

  • 22. 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, 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, 2166-2173 p.Article 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.

  • 23. 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, 1222-1230 p.Article 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;).

  • 24. 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, 344-353 p.Article 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. 

  • 25.
    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, 1-10 p.Article 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.

  • 26. 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, 531-540 p.Article 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.

  • 27. 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.
    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, 2000-2011 p.Article 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.

  • 28. 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, 3037-3046 p.Article 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.

  • 29. 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, 1866-1874 p.Article 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

  • 30. 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, 619-628 p.Article 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.

  • 31. 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, 2428-2437 p.Article 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.

  • 32. 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.

  • 33. 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, E665-E676 p.Article 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.

  • 34. 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, 5614-5624 p.Article 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.

  • 35. 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, 1018-1027 p.Article 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.

  • 36. 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, 2683-2690 p.Article 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.

  • 37. 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, 1947-1957 p.Article 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.

  • 38. 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, S133-S134 p.Article in journal (Other academic)
  • 39. 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, 389-401 p.Article 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.

  • 40. Kühn, Tilman
    et al.
    Kaaks, Rudolf
    Becker, Susen
    Eomois, Piia-Piret
    Clavel-Chapelon, Françoise
    Kvaskoff, Marina
    Dossus, Laure
    Tjønneland, Anne
    Olsen, Anja
    Overvad, Kim
    Chang-Claude, Jenny
    Lukanova, Annekatrin
    Buijsse, Brian
    Boeing, Heiner
    Trichopoulou, Antonia
    Lagiou, Pagona
    Bamia, Christina
    Masala, Giovanna
    Krogh, Vittorio
    Sacerdote, Carlotta
    Tumino, Rosario
    Mattiello, Amalia
    Buckland, Genevieve
    Sánchez, María-José
    Menéndez, Virginia
    Chirlaque, María-Dolores
    Barricarte, Aurelio
    Bueno-de-Mesquita, H Bas
    van Duijnhoven, Fränzel J B
    van Gils, Carla H
    Bakker, Marije F
    Weiderpass, Elisabete
    Skeie, Guri
    Brustad, Magritt
    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.
    Wareham, Nick
    Khaw, Kay Tee
    Travis, Ruth C
    Schmidt, Julie A
    Rinaldi, Sabina
    Romieu, Isabelle
    Gallo, Valentina
    Murphy, Neil
    Riboli, Elio
    Linseisen, Jakob
    Plasma 25-hydroxyvitamin D and the risk of breast cancer in the European prospective investigation into cancer and nutrition: A nested case-control study2013In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 133, no 7, 1689-1700 p.Article in journal (Refereed)
    Abstract [en]

    Experimental evidence suggests that vitamin D might play a role in the development of breast cancer. Although the results of case-control studies indicate that circulating 25-hydroxyvitamin D [25(OH)D] is inversely associated with the risk of breast cancer, the results of prospective studies are inconsistent. A case-control study embedded in the European Prospective Investigation into Cancer and Nutrition (EPIC) was carried out comprising 1,391 incident breast cancer cases and 1,391 controls. Multivariable conditional logistic regression models did not reveal a significant overall association between season-standardized 25(OH)D levels and the risk of breast cancer (ORQ4-Q1 [95% CI]: 1.07 [0.85-1.36], ptrend = 0.67). Moreover, 25(OH)D levels were not related to the risks of estrogen receptor positive tumors (ORQ4-Q1 [95% CI]: 0.97 [0.67-1.38], ptrend = 0.90) and estrogen receptor negative tumors (ORQ4-Q1 [95% CI]: 0.97 [0.66-1.42], ptrend = 0.98). In hormone replacement therapy (HRT) users, 25(OH)D was significantly inversely associated with incident breast cancer (ORlog2 [95% CI]: 0.62 [0.42-0.90], p = 0.01), whereas no significant association was found in HRT nonusers (ORlog2 [95% CI]: 1.14 [0.80-1.62], p = 0.48). Further, a nonsignificant inverse association was found in women with body mass indices (BMI) < 25 kg/m(2) (ORlog2 [95% CI]: 0.83 [0.67-1.03], p = 0.09), as opposed to a borderline significant positive association in women with BMI ≥ 25 kg/m(2) (ORlog2 [95% CI]: 1.30 [1.0-1.69], p = 0.05). Overall, prediagnostic levels of circulating 25(OH)D were not related to the risk of breast cancer in the EPIC study. This result is in line with findings in the majority of prospective studies and does not support a role of vitamin D in the development of breast cancer.

  • 41. Le, Nha
    et al.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Vinci, Alessio
    Prognostic and predictive markers in pancreatic adenocarcinoma2016In: Digestive and Liver Disease, ISSN 1590-8658, E-ISSN 1878-3562, Vol. 48, no 3, 223-230 p.Article, review/survey (Refereed)
    Abstract [en]

    Pancreatic ductal adenocarcinoma is characterized by a poor prognosis and a low median survival, despite improvements observed for many other solid tumours. Intensive research efforts have been undertaken during the last decades to discover new prognostic and treatment predictive biomarkers for pancreatic ductal adenocarcinoma. The mainstay of medical treatment for the disease has been the well-tolerated nucleoside analogue, gemcitabine. The only targeted agent currently used in pancreatic ductal adenocarcinoma patients is the epithelial growth factor receptor inhibitor erlotinib in combination with gemcitabine. Recently, treatment regimens such as a combination of fluorouracilleucovorin-irinotecan-oxaliplatin (FOLFIRINOX) and the combination of nab-paclitaxel with gemcitabine have been introduced for metastatic pancreatic ductal adenocarcinoma. Although these treatment regimens significantly improve survival of patients, there are no good predictive biomarkers available that can be used to identify who would benefit most from them. Therefore, the search for predictive biomarkers that would facilitate personalization of chemotherapy is highly relevant.

  • 42. LeBleu, Valerie
    et al.
    Sund, Malin
    Sugimoto, Hikaru
    Birrane, Gabriel
    Kanasaki, Keizo
    Finan, Elizabeth
    Miller, Caroline A
    Gattone, Vincent H
    McLaughlin, Heather
    Shield, Charles F
    Kalluri, Raghu
    Identification of the NC1 domain of α3 chain as critical for α3α4α5 type IV collagen network assembly2010In: Journal of Biological Chemistry, ISSN 0021-9258, E-ISSN 1083-351X, Vol. 285, no 53, 41874-41885 p.Article in journal (Refereed)
    Abstract [en]

    The network organization of type IV collagen consisting of α3, α4, and α5 chains in the glomerular basement membrane (GBM) is speculated to involve interactions of the triple helical and NC1 domain of individual α-chains, but in vivo evidence is lacking. To specifically address the contribution of the NC1 domain in the GBM collagen network organization, we generated a mouse with specific loss of α3NC1 domain while keeping the triple helical α3 chain intact by connecting it to the human α5NC1 domain. The absence of α3NC1 domain leads to the complete loss of the α4 chain. The α3 collagenous domain is incapable of incorporating the α5 chain, resulting in the impaired organization of the α3α4α5 chain-containing network. Although the α5 chain can assemble with the α1, α2, and α6 chains, such assembly is incapable of functionally replacing the α3α4α5 protomer. This novel approach to explore the assembly type IV collagen in vivo offers novel insights in the specific role of the NC1 domain in the assembly and function of GBM during health and disease.

  • 43. Leenders, Max
    et al.
    Chuang, Shu-Chun
    Dahm, Christina C
    Overvad, Kim
    Ueland, Per Magne
    Midttun, Oivind
    Vollset, Stein Emil
    Tjønneland, Anne
    Halkjaer, Jytte
    Jenab, Mazda
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Kaaks, Rudolf
    Canzian, Federico
    Boeing, Heiner
    Weikert, Cornelia
    Trichopoulou, Antonia
    Bamia, Christina
    Naska, Androniki
    Palli, Domenico
    Pala, Valeria
    Mattiello, Amalia
    Tumino, Rosario
    Sacerdote, Carlotta
    van Duijnhoven, Fränzel J B
    Peeters, Petra H M
    van Gils, Carla H
    Lund, Eiliv
    Rodriguez, Laudina
    Duell, Eric J
    Pérez, María-José Sánchez
    Molina-Montes, Esther
    Castaño, José María Huerta
    Barricarte, Aurelio
    Larrañaga, Nerea
    Johansen, Dorthe
    Lindkvist, Björn
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Ye, Weimin
    Khaw, Kay-Tee
    Wareham, Nicholas J
    Michaud, Dominique S
    Riboli, Elio
    Xun, Wei W
    Allen, Naomi E
    Crowe, Francesca L
    Bueno-de-Mesquita, H Bas
    Vineis, Paolo
    Plasma cotinine levels and pancreatic cancer in the EPIC cohort study.2012In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 131, no 4, 997-1002 p.Article in journal (Refereed)
    Abstract [en]

    Smoking is an established risk factor for pancreatic cancer, previously investigated by the means of questionnaires. Using cotinine as a biomarker for tobacco exposure allows more accurate quantitative analyses to be performed. This study on pancreatic cancer, nested within the European Prospective Investigation into Cancer and Nutrition (EPIC cohort), included 146 cases and 146 matched controls. Using liquid chromatography-mass spectrometry, plasma cotinine levels were analyzed on average 8.0 years before cancer onset (5-95% range: 2.8-12.0 years). The relation between plasma cotinine levels and pancreatic cancer was analyzed with conditional logistic regression for different levels of cotinine in a population of never and current smokers. This was also done for the self-reported number of smoked cigarettes per day at baseline. Every increase of 350 nmol/L of plasma cotinine was found to significantly elevate risk of pancreatic cancer [odds ratio (OR): 1.33, 95% confidence interval (CI): 1.11-1.60]. People with a cotinine level over 1187.8 nmol/L, a level comparable to smoking 17 cigarettes per day, have an elevated risk of pancreatic cancer, compared to people with cotinine levels below 55 nmol/L (OR: 3.66, 95% CI: 1.44-9.26). The results for self-reported smoking at baseline also show an increased risk of pancreatic cancer from cigarette smoking based on questionnaire information. People who smoke more than 30 cigarettes per day showed the highest risk compared to never smokers (OR: 4.15, 95% CI: 1.02-16.42). This study is the first to show that plasma cotinine levels are strongly related to pancreatic cancer.

  • 44.
    Lindahl, Charlotta
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Simonsson, Monika
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Thysell, Elin
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    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.
    Increased levels of macrophage-secreted Cathepsin S during Prostate Cancer progression in TRAMP mice and patients2009In: Cancer Genomics and Proteomics, ISSN ISSN 1109-6535, EISSN 1790-6245, Vol. 6, no 3, 149-159 p.Article in journal (Refereed)
    Abstract [en]

    Background: Protein expression during prostate tumour progression in transgenic TRAMP mice was studied, with the aim of identifying proteins associated with tumour progression and castration resistant tumour growth. Materials and Methods: Protein expression was compared between normal mouse prostate, primary TRAMP tumours and peripheral metastases in long-term castrated TRAMP mice using 2-dimensional differential in-gel electrophoresis and MALDI TOF/TOF analysis. Results were verified with Western blot analysis and immunohisto-chemistry in the TRAMP model and samples from patients. Results: The active form of cathepsin S (Cat S) was identified as being significantly up-regulated in poorly differentiated TRAMP tumours and in castration-resistant metastases compared to normal mouse prostate and well-differentiated tumours. Increased Cat S levels were also found in high Gleason grade tumour areas in patients. Cat S was primarily expressed by tumour-infiltrating macrophages, as shown by double staining of Cat S and CD68 expressing cells. A significantly higher number of Cat S expressing macrophages was found in castration-resistant than in hormone naïve high grade tumours in patients. No relation was found between Cat S levels and suggested Cat S regulated, matrix-derived fragments of collagen IV or laminin 5 γ2. Conclusion: Macrophage-secreted Cat S levels increase during prostate cancer progression and could be an interesting target for therapy.

  • 45. Lujan-Barroso, Leila
    et al.
    González, Carlos Alberto
    Slimani, Nadia
    Obón-Santacana, Mireia
    Ferrari, Pietro
    Freisling, Heinz
    Overvad, Kim
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Racine, Antoine
    Katzke, Verena
    Kühn, Tilman
    Tjønneland, Anne
    Olsen, Anja
    Quirós, J Ramón
    Sánchez-Cantalejo, Emilio
    Amiano, Pilar
    Navarro, Carmen
    Barricarte, Aurelio
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C
    Trichopoulou, Antonia
    Bamia, Christina
    Benetou, Vassiliki
    Saieva, Calogero
    Grioni, Sara
    Tumino, Rosario
    Vineis, Paolo
    Mattiello, Amalia
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Numans, Mattijs E
    Peeters, Petra H
    Ericson, Ulrika
    Wirfält, Elisabet
    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.
    Weiderpass, Elisabete
    Skeie, Guri
    Riboli, Elio
    Boeing, Heiner
    Duell, Eric J
    Dietary intake of acrylamide and esophageal cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort2014In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 25, no 5, 639-646 p.Article in journal (Refereed)
    Abstract [en]

    PURPOSE: The relation between dietary acrylamide intake and esophageal cancer (EC) risk, including esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), has not been consistent. We evaluated the association between dietary acrylamide intake and EAC, ESCC, and overall EC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    METHODS: Multivariate Cox proportional hazards models were used to estimate the HR and 95 % confidence interval (95 % CI). Since nonlinear relations were observed, HRs were displayed for quartiles of acrylamide intake in μg per day.

    RESULTS: After a mean follow-up of 11 years, 341 EC were identified, 142 of which were EAC, 176 ESCC, and 23 other histological types or not specified. An increase in EC risk was observed in the second and third quartiles (HRQ2vsQ1 1.75, 95 % CI 1.12-2.74; HRQ3vsQ1 1.66, 95 % CI 1.05-2.61), but not in the fourth quartile, and there was no evidence for a linear dose-response trend. HRs were similarly elevated but not statistically significant when ESCC and EAC were analyzed separately, due to the small number of cases observed. No associations were observed when quartiles were based on energy-adjusted acrylamide intake.

    CONCLUSIONS: In the EPIC cohort, an association between estimated dietary acrylamide intake and an increased risk of developing EC was observed in the middle quartiles but not in the highest quartile; however, results from other larger cohorts or consortia, and results from biomarker studies, might add to the evidence provided by this analysis, suggesting that acrylamide is not an important risk factor for EC.

  • 46.
    Lukanova, Annekatrin
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Division of Cancer Epidemiology, German Cancer Research Centre, Heidelberg, Germany.
    Becker, Susen
    Hüsing, Anika
    Schock, Helena
    Fedirko, Veronika
    Trepo, Elisabeth
    Trichopoulou, Antonia
    Bamia, Christina
    Lagiou, Pagona
    Benetou, Vassiliki
    Trichopoulos, Dimitrios
    Nöthlings, Ute
    Tjønneland, Anne
    Overvad, Kim
    Dossus, Laure
    Teucher, Birgit
    Boeing, Heiner
    Aleksandrova, Krasimira
    Palli, Domenico
    Pala, Valeria
    Panico, Salvatore
    Tumino, Rosario
    Ricceri, Fulvio
    Bueno-de-Mesquita, H Bas
    Siersema, Peter D
    Peeters, Petra M
    Quiros, Jose Ramon
    Duell, Eric J
    Molina-Montes, Esther
    Chirlaque, Maria-Dolores
    Gurrea, Aurelio Barricarte
    Dorronsoro, Miren
    Lindkvist, Björn
    Johansen, Dorthe
    Werner, Mårten
    Sund, Malin
    Khaw, Kay-Tee
    Wareham, Nick
    Key, Timothy J
    Travis, Ruth C
    Rinaldi, Sabina
    Romieu, Isabelle
    Gunter, Marc J
    Riboli, Elio
    Jenab, Mazda
    Kaaks, Rudolf
    Pre-diagnostic plasma testosterone, sex hormone binding globulin, IGF-I and hepatocellular carcinoma: etiological factors or risk markers?2014In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 134, no 1, 164-173 p.Article in journal (Refereed)
    Abstract [en]

    Elevated pre-diagnostic testosterone and insulin-like growth factor-I (IGF-I) concentrations have been proposed to increase risk of hepatocellular carcinoma (HCC). However, the metabolism of these hormones is altered as a consequence of liver damage and they may have clinical utility as HCC risk markers. A case-control study was nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort and included 125 incident HCC cases and 247 individually matched controls. Testosterone, sex hormone binding globulin (SHBG) and IGF-I were analyzed by immunoassays. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by conditional logistic regression. The area under the receiver operating curves (AUC) was calculated to assess HCC predictive ability of the tested models. After adjustments for epidemiological variables (body mass index, smoking, ethanol intake, hepatitis and diabetes) and liver damage (a score based on albumin, bilirubin, aspartate aminotransaminase, alanine aminotransaminase, gamma-glutamyltransferase and alkaline phosphatase concentrations), only SHBG remained significantly associated with risk (OR for top versus bottom tertile of 3.86 (1.32-11.3), ptrend =0.009). As a single factor SHBG had an AUC of 0.81 (0.75-0.86). A small, but significant increase in AUC was observed when SHBG was added to a model including the liver damage score and epidemiological variables (from 0.89 to 0.91, p=0.02) and a net reclassification of 0.47% (0.45-0.48). The observed associations of HCC with pre-diagnostic SHBG, free testosterone and IGF-I concentrations are in directions opposite to that expected under the etiological hypotheses. SHBG has a potential to be tested as pre-diagnostic risk marker for HCC.

  • 47. MacDonald, Brian A
    et al.
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Grant, Marianne A
    Pfaff, Kathleen L
    Holthaus, Kathryn
    Zon, Leonard I
    Kalluri, Raghu
    Zebrafish to humans: evolution of the alpha3-chain of type IV collagen and emergence of the autoimmune epitopes associated with Goodpasture syndrome.2006In: Blood, ISSN 0006-4971, E-ISSN 1528-0020, Vol. 107, no 5, 1908-1915 p.Article in journal (Refereed)
  • 48. McKenzie, Fiona
    et al.
    Ferrari, Pietro
    Freisling, Heinz
    Chajes, Veronique
    Rinaldi, Sabina
    de Batlle, Jordi
    Dahm, Christina C.
    Overvad, Kim
    Baglietto, Laura
    Dartois, Laureen
    Dossus, Laure
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Trichopoulou, Antonia
    Krogh, Vittorio
    Panico, Salvatore
    Tumino, Rosario
    Rosso, Stefano
    Bueno-de-Mesquita, H. B(As)
    May, Anne
    Peeters, Petra H.
    Weiderpass, Elisabete
    Buckland, Genevieve
    Sanchez, Maria-Jose
    Navarro, Carmen
    Ardanaz, Eva
    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.
    Ericson, Ulrika
    Wirfalt, Elisabet
    Key, Tim J.
    Travis, Ruth C.
    Gunter, Marc
    Riboli, Elio
    Vergnaud, Anne-Claire
    Romieu, Isabelle
    Healthy lifestyle and risk of breast cancer among postmenopausal women in the European Prospective Investigation into Cancer and Nutrition cohort study2015In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 136, no 11, 2640-2648 p.Article in journal (Refereed)
    Abstract [en]

    Breast cancer is the most common cancer among women and prevention strategies are needed to reduce incidence worldwide. A healthy lifestyle index score (HLIS) was generated to investigate the joint effect of modifiable lifestyle factors on postmenopausal breast cancer risk. The study included 242,918 postmenopausal women from the multinational European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, with detailed information on diet and lifestyle assessed at baseline. The HLIS was constructed from five factors (diet, physical activity, smoking, alcohol consumption and anthropometry) by assigning scores of 0-4 to categories of each component, for which higher values indicate healthier behaviours. Hazard ratios (HR) were estimated by Cox proportional regression models. During 10.9 years of median follow-up, 7,756 incident breast cancer cases were identified. There was a 3% lower risk of breast cancer per point increase of the HLIS. Breast cancer risk was inversely associated with a high HLIS when fourth versus second (reference) categories were compared [adjusted HR=0.74; 95% confidence interval (CI): 0.66-0.83]. The fourth versus the second category of the HLIS was associated with a lower risk for hormone receptor double positive (adjusted HR=0.81, 95% CI: 0.67-0.98) and hormone receptor double negative breast cancer (adjusted HR=0.60, 95% CI: 0.40-0.90). Findings suggest having a high score on an index of combined healthy behaviours reduces the risk of developing breast cancer among postmenopausal women. Programmes which engage women in long term health behaviours should be supported. What's new? How much does behavior really affect cancer risk? These authors set out to measure just that. First, they created a Healthy Lifestyle Index, which quantified five modifiable behaviors, such as smoking and physical activity. Then, using data from the European Prospective Investigation into Cancer and Nutrition (EPIC), they assigned each participant a score between 0 and 4 on each of the behaviors. It turned out that with each point added to a person's Healthy Lifestyle Index score, breast cancer risk fell by 3%, suggesting that public programs to help women maintain these behaviors could be worthwhile for cancer prevention.

  • 49. Michailidou, Kyriaki
    et al.
    Beesley, Jonathan
    Lindstrom, Sara
    Canisius, Sander
    Dennis, Joe
    Lush, Michael J.
    Maranian, Mel J.
    Bolla, Manjeet K.
    Wang, Qin
    Shah, Mitul
    Perkins, Barbara J.
    Czene, Kamila
    Eriksson, Mikael
    Darabi, Hatef
    Brand, Judith S.
    Bojesen, Stig E.
    Nordestgaard, Borge G.
    Flyger, Henrik
    Nielsen, Sune F.
    Rahman, Nazneen
    Turnbull, Clare
    Fletcher, Olivia
    Peto, Julian
    Gibson, Lorna
    dos-Santos-Silva, Isabel
    Chang-Claude, Jenny
    Flesch-Janys, Dieter
    Rudolph, Anja
    Eilber, Ursula
    Behrens, Sabine
    Nevanlinna, Heli
    Muranen, Taru A.
    Aittomaki, Kristiina
    Blomqvist, Carl
    Khan, Sofia
    Aaltonen, Kirsimari
    Ahsan, Habibul
    Kibriya, Muhammad G.
    Whittemore, Alice S.
    John, Esther M.
    Malone, Kathleen E.
    Gammon, Marilie D.
    Santella, Regina M.
    Ursin, Giske
    Makalic, Enes
    Schmidt, Daniel F.
    Casey, Graham
    Hunter, David J.
    Gapstur, Susan M.
    Gaudet, Mia M.
    Diver, W. Ryan
    Haiman, Christopher A.
    Schumacher, Fredrick
    Henderson, Brian E.
    Le Marchand, Loic
    Berg, Christine D.
    Chanock, Stephen J.
    Figueroa, Jonine
    Hoover, Robert N.
    Lambrechts, Diether
    Neven, Patrick
    Wildiers, Hans
    van Limbergen, Erik
    Schmidt, Marjanka K.
    Broeks, Annegien
    Verhoef, Senno
    Cornelissen, Sten
    Couch, Fergus J.
    Olson, Janet E.
    Hallberg, Emily
    Vachon, Celine
    Waisfisz, Quinten
    Meijers-Heijboer, Hanne
    Adank, Muriel A.
    van der Luijt, Rob B.
    Li, Jingmei
    Liu, Jianjun
    Humphreys, Keith
    Kang, Daehee
    Choi, Ji-Yeob
    Park, Sue K.
    Yoo, Keun-Young
    Matsuo, Keitaro
    Ito, Hidemi
    Iwata, Hiroji
    Tajima, Kazuo
    Guenel, Pascal
    Truong, Therese
    Mulot, Claire
    Sanchez, Marie
    Burwinkel, Barbara
    Marme, Frederik
    Surowy, Harald
    Sohn, Christof
    Wu, Anna H.
    Tseng, Chiu-chen
    Van den Berg, David
    Stram, Daniel O.
    Gonzalez-Neira, Anna
    Benitez, Javier
    Zamora, M. Pilar
    Arias Perez, Jose Ignacio
    Shu, Xiao-Ou
    Lu, Wei
    Gao, Yu-Tang
    Cai, Hui
    Cox, Angela
    Cross, Simon S.
    Reed, Malcolm W. R.
    Andrulis, Irene L.
    Knight, Julia A.
    Glendon, Gord
    Mulligan, Anna Marie
    Sawyer, Elinor J.
    Tomlinson, Ian
    Kerin, Michael J.
    Miller, Nicola
    Lindblom, Annika
    Margolin, Sara
    Teo, Soo Hwang
    Yip, Cheng Har
    Taib, Nur Aishah Mohd
    Tan, Gie-Hooi
    Hooning, Maartje J.
    Hollestelle, Antoinette
    Martens, John W. M.
    Collee, J. Margriet
    Blot, William
    Signorello, Lisa B.
    Cai, Qiuyin
    Hopper, John L.
    Southey, Melissa C.
    Tsimiklis, Helen
    Apicella, Carmel
    Shen, Chen-Yang
    Hsiung, Chia-Ni
    Wu, Pei-Ei
    Hou, Ming-Feng
    Kristensen, Vessela N.
    Nord, Silje
    Alnaes, Grethe I. Grenaker
    Giles, Graham G.
    Milne, Roger L.
    McLean, Catriona
    Canzian, Federico
    Trichopoulos, Dimitrios
    Peeters, Petra
    Lund, Eiliv
    Sund, Malin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences.
    Khaw, Kay-Tee
    Gunter, Marc J.
    Palli, Domenico
    Mortensen, Lotte Maxild
    Dossus, Laure
    Huerta, Jose-Maria
    Meindl, Alfons
    Schmutzler, Rita K.
    Sutter, Christian
    Yang, Rongxi
    Muir, Kenneth
    Lophatananon, Artitaya
    Stewart-Brown, Sarah
    Siriwanarangsan, Pornthep
    Hartman, Mikael
    Miao, Hui
    Chia, Kee Seng
    Chan, Ching Wan
    Fasching, Peter A.
    Hein, Alexander
    Beckmann, Matthias W.
    Haeberle, Lothar
    Brenner, Hermann
    Dieffenbach, Aida Karina
    Arndt, Volker
    Stegmaier, Christa
    Ashworth, Alan
    Orr, Nick
    Schoemaker, Minouk J.
    Swerdlow, Anthony J.
    Brinton, Louise
    Garcia-Closas, Montserrat
    Zheng, Wei
    Halverson, Sandra L.
    Shrubsole, Martha
    Long, Jirong
    Goldberg, Mark S.
    Labreche, France
    Dumont, Martine
    Winqvist, Robert
    Pylkas, Katri
    Jukkola-Vuorinen, Arja
    Grip, Mervi
    Brauch, Hiltrud
    Hamann, Ute
    Bruening, Thomas
    Radice, Paolo
    Peterlongo, Paolo
    Manoukian, Siranoush
    Bernard, Loris
    Bogdanova, Natalia V.
    Doerk, Thilo
    Mannermaa, Arto
    Kataja, Vesa
    Kosma, Veli-Matti
    Hartikainen, Jaana M.
    Devilee, Peter
    Tollenaar, Robert A. E. M.
    Seynaeve, Caroline
    Van Asperen, Christi J.
    Jakubowska, Anna
    Lubinski, Jan
    Jaworska, Katarzyna
    Huzarski, Tomasz
    Sangrajrang, Suleeporn
    Gaborieau, Valerie
    Brennan, Paul
    Mckay, James
    Slager, Susan
    Toland, Amanda E.
    Ambrosone, Christine B.
    Yannoukakos, Drakoulis
    Kabisch, Maria
    Torres, Diana
    Neuhausen, Susan L.
    Anton-Culver, Hoda
    Luccarini, Craig
    Baynes, Caroline
    Ahmed, Shahana
    Healey, Catherine S.
    Tessier, Daniel C.
    Vincent, Daniel
    Bacot, Francois
    Pita, Guillermo
    Rosario Alonso, M.
    Alvarez, Nuria
    Herrero, Daniel
    Simard, Jacques
    Pharoah, Paul P. D. P.
    Kraft, Peter
    Dunning, Alison M.
    Chenevix-Trench, Georgia
    Hall, Per
    Easton, Douglas F.
    Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer2015In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 47, no 4, 373-U127 p.Article in journal (Refereed)
    Abstract [en]

    Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining similar to 14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 x 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

  • 50. Michaud, Dominique S
    et al.
    Izard, Jacques
    Wilhelm-Benartzi, Charlotte S
    You, Doo-Ho
    Grote, Verena A
    Tjønneland, Anne
    Dahm, Christina C
    Overvad, Kim
    Jenab, Mazda
    Fedirko, Veronika
    Boutron-Ruault, Marie Christine
    Clavel-Chapelon, Françoise
    Racine, Antoine
    Kaaks, Rudolf
    Boeing, Heiner
    Foerster, Jana
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Sacerdote, Carlotta
    Sieri, Sabina
    Palli, Domenico
    Tumino, Rosario
    Panico, Salvatore
    Siersema, Peter D
    Peeters, Petra Hm
    Lund, Eiliv
    Barricarte, Aurelio
    Huerta, José-María
    Molina-Montes, Esther
    Dorronsoro, Miren
    Quirós, J Ramón
    Duell, Eric J
    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. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Lindkvist, Björn
    Johansen, Dorthe
    Khaw, Kay-Tee
    Wareham, Nick
    Travis, Ruth C
    Vineis, Paolo
    Bueno-de-Mesquita, H Bas
    Riboli, Elio
    Plasma antibodies to oral bacteria and risk of pancreatic cancer in a large European prospective cohort study2013In: Gut, ISSN 0017-5749, E-ISSN 1468-3288, Vol. 62, no 12, 1764-1770 p.Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: Examine the relationship between antibodies to 25 oral bacteria and pancreatic cancer risk in a prospective cohort study. DESIGN: We measured antibodies to oral bacteria in prediagnosis blood samples from 405 pancreatic cancer cases and 416 matched controls, nested within the European Prospective Investigation into Cancer and Nutrition study. Analyses were conducted using conditional logistic regression and additionally adjusted for smoking status and body mass index. RESULTS: Individuals with high levels of antibodies against Porphyromonas gingivalis ATTC 53978, a pathogenic periodontal bacteria, had a twofold higher risk of pancreatic cancer than individuals with lower levels of these antibodies (OR 2.14; 95% CI 1.05 to 4.36; >200 ng/ml vs ≤200 ng/ml). To explore the association with commensal (non-pathogenic) oral bacteria, we performed a cluster analysis and identified two groups of individuals, based on their antibody profiles. A cluster with overall higher levels of antibodies had a 45% lower risk of pancreatic cancer than a cluster with overall lower levels of antibodies (OR 0.55; 95% CI 0.36 to 0.83). CONCLUSIONS: Periodontal disease might increase the risk for pancreatic cancer. Moreover, increased levels of antibodies against specific commensal oral bacteria, which can inhibit growth of pathogenic bacteria, might reduce the risk of pancreatic cancer. Studies are needed to determine whether oral bacteria have direct effects on pancreatic cancer pathogenesis or serve as markers of the immune response.

123 1 - 50 of 107
CiteExportLink to result list
Permanent link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf