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  • 51. Antoniou, Antonis C
    et al.
    Kartsonaki, Christiana
    Sinilnikova, Olga M
    Soucy, Penny
    McGuffog, Lesley
    Healey, Sue
    Lee, Andrew
    Peterlongo, Paolo
    Manoukian, Siranoush
    Peissel, Bernard
    Zaffaroni, Daniela
    Cattaneo, Elisa
    Barile, Monica
    Pensotti, Valeria
    Pasini, Barbara
    Dolcetti, Riccardo
    Giannini, Giuseppe
    Putignano, Anna Laura
    Varesco, Liliana
    Radice, Paolo
    Mai, Phuong L
    Greene, Mark H
    Andrulis, Irene L
    Glendon, Gord
    Ozcelik, Hilmi
    Thomassen, Mads
    Gerdes, Anne-Marie
    Kruse, Torben A
    Birk Jensen, Uffe
    Crüger, Dorthe G
    Caligo, Maria A
    Laitman, Yael
    Milgrom, Roni
    Kaufman, Bella
    Paluch-Shimon, Shani
    Friedman, Eitan
    Loman, Niklas
    Harbst, Katja
    Lindblom, Annika
    Arver, Brita
    Ehrencrona, Hans
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nathanson, Katherine L
    Domchek, Susan M
    Rebbeck, Timothy
    Jakubowska, Ania
    Lubinski, Jan
    Gronwald, Jacek
    Huzarski, Tomasz
    Byrski, Tomasz
    Cybulski, Cezary
    Gorski, Bohdan
    Osorio, Ana
    Ramón y Cajal, Teresa
    Fostira, Florentia
    Andrés, Raquel
    Benitez, Javier
    Hamann, Ute
    Hogervorst, Frans B
    Rookus, Matti A
    Hooning, Maartje J
    Nelen, Marcel R
    van der Luijt, Rob B
    van Os, Theo A M
    van Asperen, Christi J
    Devilee, Peter
    Meijers-Heijboer, Hanne E J
    Garcia, Encarna B Gómez
    Peock, Susan
    Cook, Margaret
    Frost, Debra
    Platte, Radka
    Leyland, Jean
    Evans, D Gareth
    Lalloo, Fiona
    Eeles, Ros
    Izatt, Louise
    Adlard, Julian
    Davidson, Rosemarie
    Eccles, Diana
    Ong, Kai-ren
    Cook, Jackie
    Douglas, Fiona
    Paterson, Joan
    Kennedy, M John
    Miedzybrodzka, Zosia
    Godwin, Andrew
    Stoppa-Lyonnet, Dominique
    Buecher, Bruno
    Belotti, Muriel
    Tirapo, Carole
    Mazoyer, Sylvie
    Barjhoux, Laure
    Lasset, Christine
    Leroux, Dominique
    Faivre, Laurence
    Bronner, Myriam
    Prieur, Fabienne
    Nogues, Catherine
    Rouleau, Etienne
    Pujol, Pascal
    Coupier, Isabelle
    Frénay, Marc
    Hopper, John L
    Daly, Mary B
    Terry, Mary B
    John, Esther M
    Buys, Saundra S
    Yassin, Yosuf
    Miron, Alexander
    Goldgar, David
    Singer, Christian F
    Tea, Muy-Kheng
    Pfeiler, Georg
    Dressler, Anne Catharina
    Hansen, Thomas v O
    Jønson, Lars
    Ejlertsen, Bent
    Barkardottir, Rosa Bjork
    Kirchhoff, Tomas
    Offit, Kenneth
    Piedmonte, Marion
    Rodriguez, Gustavo
    Small, Laurie
    Boggess, John
    Blank, Stephanie
    Basil, Jack
    Azodi, Masoud
    Toland, Amanda Ewart
    Montagna, Marco
    Tognazzo, Silvia
    Agata, Simona
    Imyanitov, Evgeny
    Janavicius, Ramunas
    Lazaro, Conxi
    Blanco, Ignacio
    Pharoah, Paul D P
    Sucheston, Lara
    Karlan, Beth Y
    Walsh, Christine S
    Olah, Edith
    Bozsik, Aniko
    Teo, Soo-Hwang
    Seldon, Joyce L
    Beattie, Mary S
    van Rensburg, Elizabeth J
    Sluiter, Michelle D
    Diez, Orland
    Schmutzler, Rita K
    Wappenschmidt, Barbara
    Engel, Christoph
    Meindl, Alfons
    Ruehl, Ina
    Varon-Mateeva, Raymonda
    Kast, Karin
    Deissler, Helmut
    Niederacher, Dieter
    Arnold, Norbert
    Gadzicki, Dorothea
    Schönbuchner, Ines
    Caldes, Trinidad
    de la Hoya, Miguel
    Nevanlinna, Heli
    Aittomäki, Kristiina
    Dumont, Martine
    Chiquette, Jocelyne
    Tischkowitz, Marc
    Chen, Xiaoqing
    Beesley, Jonathan
    Spurdle, Amanda B
    Neuhausen, Susan L
    Chun Ding, Yuan
    Fredericksen, Zachary
    Wang, Xianshu
    Pankratz, Vernon S
    Couch, Fergus
    Simard, Jacques
    Easton, Douglas F
    Chenevix-Trench, Georgia
    Common alleles at 6q25.1 and 1p11.2 are associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers2011In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 20, no 16, p. 3304-3321Article in journal (Refereed)
    Abstract [en]

    Two single nucleotide polymorphisms (SNPs) at 6q25.1, near the ESR1 gene, have been implicated in the susceptibility to breast cancer for Asian (rs2046210) and European women (rs9397435). A genome-wide association study in Europeans identified two further breast cancer susceptibility variants: rs11249433 at 1p11.2 and rs999737 in RAD51L1 at 14q24.1. Although previously identified breast cancer susceptibility variants have been shown to be associated with breast cancer risk for BRCA1 and BRCA2 mutation carriers, the involvement of these SNPs to breast cancer susceptibility in mutation carriers is currently unknown. To address this, we genotyped these SNPs in BRCA1 and BRCA2 mutation carriers from 42 studies from the Consortium of Investigators of Modifiers of BRCA1/2. In the analysis of 14 123 BRCA1 and 8053 BRCA2 mutation carriers of European ancestry, the 6q25.1 SNPs (r(2) = 0.14) were independently associated with the risk of breast cancer for BRCA1 mutation carriers [hazard ratio (HR) = 1.17, 95% confidence interval (CI): 1.11-1.23, P-trend = 4.5 × 10(-9) for rs2046210; HR = 1.28, 95% CI: 1.18-1.40, P-trend = 1.3 × 10(-8) for rs9397435], but only rs9397435 was associated with the risk for BRCA2 carriers (HR = 1.14, 95% CI: 1.01-1.28, P-trend = 0.031). SNP rs11249433 (1p11.2) was associated with the risk of breast cancer for BRCA2 mutation carriers (HR = 1.09, 95% CI: 1.02-1.17, P-trend = 0.015), but was not associated with breast cancer risk for BRCA1 mutation carriers (HR = 0.97, 95% CI: 0.92-1.02, P-trend = 0.20). SNP rs999737 (RAD51L1) was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers (P-trend = 0.27 and 0.30, respectively). The identification of SNPs at 6q25.1 associated with breast cancer risk for BRCA1 mutation carriers will lead to a better understanding of the biology of tumour development in these women.

  • 52. Arason, Adalgeir
    et al.
    Gunnarsson, Haukur
    Johannesdottir, Gudrun
    Jonasson, Kristjan
    Bendahl, Pär-Ola
    Gillanders, Elizabeth M
    Agnarsson, Bjarni A
    Jönsson, Göran
    Pylkäs, Katri
    Mustonen, Aki
    Heikkinen, Tuomas
    Aittomäki, Kristiina
    Blomqvist, Carl
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Johannsson, Oskar TH
    Møller, Pål
    Winqvist, Robert
    Nevanlinna, Heli
    Borg, Åke
    Barkardottir, Rosa B
    Genome-wide search for breast cancer linkage in large Icelandic non-BRCA1/2 families2010In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 12, no 4, p. R50-Article in journal (Refereed)
    Abstract [en]

    Chromosomes 2p, 6q and 14q are candidate sites for genes contributing together to high breast cancer risk. A polygenic model is supported, suggesting the joint effect of genes in contributing to breast cancer risk to be rather common in non-BRCA1/2 families. For genetic counselling it would seem important to resolve the mode of genetic interaction.

  • 53. Armstrong, Andrew J.
    et al.
    Anand, Aseem
    Edenbrandt, Lars
    Bondesson, Eva
    Bjartell, Anders
    Widmark, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sternberg, Cora N.
    Pili, Roberto
    Tuvesson, Helen
    Nordle, Örjan
    Carducci, Michael A.
    Morris, Michael J.
    Phase 3 Assessment of the Automated Bone Scan Index as a Prognostic Imaging Biomarker of Overall Survival in Men With Metastatic Castration-Resistant Prostate Cancer: A Secondary Analysis of a Randomized Clinical Trial2018In: JAMA Oncology, ISSN 2374-2437, E-ISSN 2374-2445, Vol. 4, no 7, p. 944-951Article in journal (Refereed)
    Abstract [en]

    Importance: Prostate cancer commonly metastasizes to bone, and bone metastases are associated with pathologic fractures, pain, and reduced survival. Bone disease is routinely visualized using the technetium Tc 99m(Tc-99m) bone scan; however, the standard interpretation of bone scan data relies on subjective manual assessment of counting metastatic lesion numbers. There is an unmet need for an objective and fully quantitative assessment of bone scan data.

    Objective: To clinically assess in a prospectively defined analysis plan of a clinical trial the automated Bone Scan Index (aBSI) as an independent prognostic determinant of overall survival (OS) in men with metastatic castration-resistant prostate cancer (mCRPC).

    Design, Setting, and Participants: This investigationwas a prospectively planned analysis of the aBSI in a phase 3 multicenter randomized, double-blind, placebo-controlled clinical trial of tasquinimod (10TASQ10). Men with bone metastatic chemotherapy-naive CRPC were recruited at 241 sites in 37 countries between March 2011 and August 2015. The statistical analysis plan to clinically evaluate the aBSI was prospectively defined and locked before unmasking of the 10TASQ10 study. The analysis of aBSI was conducted between May 25, 2016, and June 3, 2017.

    Main Outcomes and Measures: The associations of baseline aBSI with OS, radiographic progression-free survival (rPFS), time to symptomatic progression, and time to opiate use for cancer pain.

    Results: Of the total 1245 men enrolled, 721 were evaluable for the aBSI. The mean (SD) age (available for 719 men) was 70.6 (8.0) years (age range, 47-90 years). The aBSI population was representative of the total study population based on baseline characteristics. The aBSI (median, 1.07; range, 0-32.60) was significantly associated with OS (hazard ratio [HR], 1.20; 95% CI, 1.14-1.26; P < .001). The median OS by aBSI quartile (lowest to highest) was 34.7, 27.3, 21.7, and 13.3 months, respectively. The discriminative ability of the aBSI (C index, 0.63) in prognosticating OS was significantly higher than that of the manual lesion counting (C index, 0.60) (P = .03). In a multivariable survival model, a higher aBSI remained independently associated with OS (HR, 1.06; 95% CI, 1.01-1.11; P = .03). A higher aBSI was also independently associated with time to symptomatic progression (HR, 1.18; 95% CI, 1.13-1.23; P < .001) and time to opiate use for cancer pain (HR, 1.21; 95% CI, 1.14-1.30; P < .001).

    Conclusions and Relevance: To date, this investigation is the largest prospectively analyzed study to validate the aBSI as an independent prognostic imaging biomarker of survival in mCRPC. These data support the prognostic utility of the aBSI as an objective imaging biomarker in the design and eligibility of clinical trials of systemic therapies for patients with mCRPC.

  • 54. Arslan, Alan A.
    et al.
    Koenig, Karen L.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Afanasyeva, Yelena
    Shore, Roy E.
    Chen, Yu
    Lundin, Eva
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Toniolo, Paolo
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Zeleniuch-Jacquotte, Anne
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Circulating Estrogen Metabolites and Risk of Breast Cancer in Postmenopausal Women2014In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, no 7, p. 1290-1297Article in journal (Refereed)
    Abstract [en]

    Background: It has been hypothesized that predominance of the 2-hydroxylation estrogen metabolism pathway over the 16 alpha-hydroxylation pathway may be inversely associated with breast cancer risk. Methods: We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone (2-OHE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), and the 2-OHE1: 16 alpha-OHE1 ratio in a case-control study of postmenopausal women nested within two prospective cohorts: the New York University Women's Health Study (NYUWHS) and the Northern Sweden Mammary Screening Cohort (NSMSC), with adjustment for circulating levels of estrone, and additional analyses by tumor estrogen receptor (ER) status. Levels of 2-OHE1 and 16 alpha-OHE1 were measured using ESTRAMET 2/16 assay in stored serum or plasma samples from 499 incident breast cancer cases and 499 controls, who were matched on cohort, age, and date of blood donation. Results: Overall, no significant associations were observed between breast cancer risk and circulating levels of 2-OHE1, 16 alpha-OHE1, or their ratio in either cohort and in combined analyses. For 2-OHE1, there was evidence of heterogeneity by ER status in models adjusting for estrone (P <= 0.03). We observed a protective association of 2-OHE1 with ER + breast cancer [multivariate-adjusted OR for a doubling of 2-OHE1, 0.67 (95% confidence interval [CI], 0.48-0.94; P = 0.02)]. Conclusions: In this study, higher levels of 2-OHE1 were associated with reduced risk of ER + breast cancer in postmenopausal women after adjustment for circulating estrone. Impact: These results suggest that taking into account the levels of parent estrogens and ER status is important in studies of estrogen metabolites and breast cancer.

  • 55. Ask, Anders
    et al.
    Björk-Eriksson, Thomas
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Blomquist, Erik
    Glimelius, Bengt
    The potential of proton beam radiation therapy in head and neck cancer.2005In: Acta Oncol, ISSN 0284-186X, Vol. 44, no 8, p. 876-880Article in journal (Refereed)
  • 56.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Malmström, Annika
    Blomquist, Erik
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Överlevnanden vid maligna gliom har ökat senaste tio åren. Analys av kvalitetsregisterdata.2012In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 109, no 17-18, p. 875-878Article in journal (Refereed)
    Abstract [en]

    The annual incidence rate of high grade malignant glioma (WHO grade III-IV) in Sweden is approximately 400 patients. The objective for the Swedish National CNS-tumor Group is to lay a foundation for research efforts and facilitate implementation and assessment of therapeutic strategies and health care for this patient group. In the analyses the diagnoses of high grade malignant gliomas are compared for the years 1999-2003, 2004-2006 and 2007-2009 for the Northern Region, the Uppsala Region and the South-east Region of Sweden, a population of 1844 patients. Survival was estimated from Kaplan-Meier survival curves, and a log-rank test was performed to assess whether the survival curves differed. The crude hazard ratio between years of diagnosis was estimated from a Cox regression model. Median survival for all patients 2004-2006 was 10.0 months (95 % confidence interval (CI) 8.9-10.9) compared to 8.1 months 1999-2003 (95 % CI 7.3-8.8). For patients 60-69 years of age almost a doubling of the survival rate has occurred during the last decade. Medan survival has increased from 5.8 months (95 % CI 5.1-7.5) 1999-2003 to 8.5 months (95 % CI 7.0-10.3) for 2004-2006 and to 10.5 months (95 % CI 9.0-12.6) for 2007-2009. Concomitant radiochemotherapy, but also the development of neurosurgical and radiotheraputic techniques and a more active therapeutic attitude, including the older patient groups, have probably contributed to the improved survival rate. A national population based registry, with a close to 100% registration compliance for important diagnostic and outcome parameters is probably an efficient instrument for evaluation of quality measures and implementation of new therapeutic strategies.

  • 57.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Danfors, T
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    PET response and tumor stabilization under erlotinib and bevacizumab treatment of an intracranial lesion non-invasively diagnosed as likely chordoma2011In: Clinical Neuropathology, ISSN 0722-5091, Vol. 30, no 5, p. 242-246Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: Chordoma is a rare and a slow-growing tumor originating from the notochord and commonly localized in the skull base. Surgery and occasionally radiotherapy have emerged as the treatments of choice. In the relapsed situations available treatment options are strictly limited; however, recently molecularly targeted agents have been proposed to be of potential beneficial value. THE CASE: A 63-year-old male presenting with seizures and an extradural mass in the left brain hemisphere. An attempt to resect the tumor was followed by severe bradycardia when manipulating with the dura and therefore discontinued. It was considered too hazardous even to take a biopsy specimen. The tumor was considered radiologically and macroscopically as a chordoma. As the tumor progressed after radiotherapy, chemotherapy with erlotinib in combination with cetuximab was initiated. This treatment was interrupted due to progressive disease and toxicity. However, combination treatment with erlotinib and bevacizumab normalized the uptake of [11C]methionine PET signal and resulted in a slight tumor shrinkage on MRI. The patient is still (March 2011) free of symptoms, without cranial nerve deficits or seizures. DISCUSSION: This report shows that erlotinib and bevacizumab in combination may completely quench the transport of the essential amino acid methionine to a treatment refractory intracranial tumor bearing radiological and clinical characteristics of a chordoma. Further studies are necessary to establish this strategy as a treatment option for this indication.

  • 58.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Axelsson, Jan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergström, Åsa
    Kasper, Maria
    Ögren, Margareta
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Toftgård, Rune
    Riklund, Katrine Åhlström
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Early and persisting response to vismodegib in a patient with bone metastasizing medulloblastoma2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 4, p. 862-865Article in journal (Refereed)
  • 59.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kvarnbrink, Samuel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Synergistic Killing of Glioblastoma Stem-like Cells by Bortezomib and HADC Inhibitors.2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 7, p. 2407-2413Article in journal (Refereed)
    Abstract [en]

    Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.

  • 60.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kvarnbrink, Samuel
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Holmlund, Camilla
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bergenheim, Tommy
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hedman, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Synergistic killing of Glioblastoma Stem-like cells by Bortezomib and HDAC Inhibitors2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 7 ; Special Issue, p. 2407-2413Article in journal (Refereed)
    Abstract [en]

    Background: The malignant brain tumour glioblastoma is a devastating disease that remains a therapeutic challenge. Materials and Methods: Effects of combinations of the US Food and Drug Administation (FDA) approved proteasome inhibitor bortezomib and the histone deacetylase (HDAC) inhibitors vorinostat, valproic acid and sodium phenylbutyrate were studied on primary glioblastoma stem cell lines and conventional glioblastoma cell lines. Cell survival, proliferation and death were analyzed by fluorometric microculture cytotoxicity assay (FMCA), propidium iodide labeling and flow cytometry, and cell cloning through limiting dilution and live-cell bright-field microscopy. Results: Bortezomib and the HDAC inhibitors showed synergistic cell killing at clinically relevant drug concentrations, while the conventional cell lines cultured in serum-containing medium were relatively resistant to the same treatments. Conclusion: These findings of synergistic glioblastoma stem cell killing by bortezomib and three different FDA-approved HDAC inhibitors confirm and expand previous observations on co-operative effects between these classes of drugs.

  • 61.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Malmstrom, Annika
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Blomquist, Erik
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Considerable improvement in survival for patients aged 60-84 years with high grade malignant gliomas - Data from the Swedish Brain Tumour Population-based Registry2013In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 52, no 5, p. 1043-1046Article in journal (Refereed)
  • 62.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Malmström, Annika
    Bergqvist, Michael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Björ, Ove
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brain tumors in Sweden: Data from a population-based registry 1999-20122015In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 3, p. 377-384Article in journal (Refereed)
    Abstract [en]

    Background. The Swedish brain tumor registry has, since it was launched in 1999, provided significant amounts of data on histopathological diagnoses and on important aspects of surgical and medical management of these patients. The purpose is mainly quality control, but also as a resource for research.

    Methods. Three Swedish healthcare regions, constituting 40% of the Swedish population, have had an almost complete registration. The following parameters are registered: diagnosis according to SNOMED/WHO classification, symptoms, performance status, pre- and postoperative radiology, tumor size and localization, extent of surgery and occurrence of postoperative complications, postoperative treatment, such as radiotherapy and/or chemotherapy, other treatments, complications and toxicity, occurrence of reoperation/s, participation in clinical trials, multidisciplinary conferences and availability of a contact nurse.

    Results. Surgical radicality has been essentially constant, whereas the use of early (within 72 hours) postoperative CT and MRI has increased, especially for high-grade glioma, which is a reflection of quality of surgery. Survival of patients with high-grade glioma has increased, especially in the age group 60-69. Patients aged 18-39 years had a five-year survival of 40%. Waiting times for the pathological report has been slightly prolonged. Geographical differences do exist for some of the variables.

    Conclusion. Population-based registration is valuable for assessment of clinical management, which could have impact on patient care. As a result of short survival and/or the propensity to affect cognitive functions this patient group has considerable difficulties to make their voices heard in society. We therefore believe that a report like the present one can contribute to the spread of knowledge and increase the awareness for this patient group among caregivers and policy makers.

  • 63.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Garpebring, Anders
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Hauksson, Jon
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Brynolfsson, Patrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Karlsson, Mikael
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Evaluation of advanced MR techniques for development of early biomarkers for treatment efficacy in malignant brain tumors2010Conference paper (Refereed)
  • 64.
    Asklund, Thomas
    et al.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sandström, Maria
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Shahidi, Saeed
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Riklund, Katrine
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Diagnostic Radiology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Durable stabilization of three chordoma cases by bevacizumab and erlotinib2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 7, p. 980-984Article in journal (Refereed)
  • 65. Assi, Nada
    et al.
    Gunter, Marc J.
    Thomas, Duncan C.
    Leitzmann, Michael
    Stepien, Magdalena
    Chajès, Véronique
    Philip, Thierry
    Vineis, Paolo
    Bamia, Christina
    Boutron-Ruault, Marie-Christine
    Sandanger, Torkjel M.
    Molinuevo, Amaia
    Boshuizen, Hendriek
    Sundkvist, Anneli
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kühn, Tilman
    Travis, Ruth
    Overvad, Kim
    Riboli, Elio
    Scalbert, Augustin
    Jenab, Mazda
    Viallon, Vivian
    Ferrari, Pietro
    Metabolic signature of healthy lifestyle and its relation with risk of hepatocellular carcinoma in a large European cohort2018In: American Journal of Clinical Nutrition, ISSN 0002-9165, E-ISSN 1938-3207, Vol. 108, no 1, p. 117-126Article in journal (Refereed)
    Abstract [en]

    Background: Studies using metabolomic data have identified metabolites from several compound classes that are associated with disease-related lifestyle factors.

    Objective: In this study, we identified metabolic signatures reflecting lifestyle patterns and related them to the risk of hepatocellular carcinoma (HCC) in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    Design: Within a nested case-control study of 147 incident HCC cases and 147 matched controls, partial least squares (PLS) analysis related 7 modified healthy lifestyle index (HLI) variables (diet, BMI, physical activity, lifetime alcohol, smoking, diabetes, and hepatitis) to 132 targeted serum-measured metabolites and a liver function score. The association between the resulting PLS scores and HCC risk was examined in multivariable conditional logistic regression models, where ORs and 95% CIs were computed.

    Results: The lifestyle component's PLS score was negatively associated with lifetime alcohol, BMI, smoking, and diabetes, and positively associated with physical activity. Its metabolic counterpart was positively related to the metabolites sphingomyelin (SM) (OH) C14:1, C16:1, and C22:2, and negatively related to glutamate, hexoses, and the diacyl-phosphatidylcholine PC aaC32:1. The lifestyle and metabolomics components were inversely associated with HCC risk, with the ORs for a 1-SD increase in scores equal to 0.53 (95% CI: 0.38, 0.74) and 0.28 (0.18, 0.43), and the associated AUCs equal to 0.64 (0.57, 0.70) and 0.74 (0.69, 0.80), respectively.

    Conclusions: This study identified a metabolic signature reflecting a healthy lifestyle pattern which was inversely associated with HCC risk. The metabolic profile displayed a stronger association with HCC than did the modified HLI derived from questionnaire data. Measuring a specific panel of metabolites may identify strata of the population at higher risk for HCC and can add substantial discrimination compared with questionnaire data. This trial was registered at clinicaltrials.gov as NCT03356535.

  • 66. Assi, Nada
    et al.
    Thomas, Duncan C.
    Leitzmann, Michael
    Stepien, Magdalena
    Chajès, Véronique
    Philip, Thierry
    Vineis, Paolo
    Bamia, Christina
    Boutron-Ruault, Marie-Christine
    Sandanger, Torkjel M.
    Molinuevo, Amaia
    Boshuizen, Hendriek C.
    Sundkvist, Anneli
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Kühn, Tilman
    Travis, Ruth C.
    Overvad, Kim
    Riboli, Elio
    Gunter, Marc J.
    Scalbert, Augustin
    Jenab, Mazda
    Ferrari, Pietro
    Viallon, Vivian
    Are Metabolic Signatures Mediating the Relationship between Lifestyle Factors and Hepatocellular Carcinoma Risk? Results from a Nested Case–Control Study in EPIC2018In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 27, no 5, p. 531-540Article in journal (Refereed)
    Abstract [en]

    Background: The "meeting-in-the-middle" (MITM) is a principle to identify exposure biomarkers that are also predictors of disease. The MITM statistical framework was applied in a nested case-control study of hepatocellular carcinoma (HCC) within European Prospective Investigation into Cancer and Nutrition (EPIC), where healthy lifestyle index (HLI) variables were related to targeted serum metabolites.

    Methods: Lifestyle and targeted metabolomic data were available from 147 incident HCC cases and 147 matched controls. Partial least squares analysis related 7 lifestyle variables from a modified HLI to a set of 132 serum-measured metabolites and a liver function score. Mediation analysis evaluated whether metabolic profiles mediated the relationship between each lifestyle exposure and HCC risk.

    Results: Exposure-related metabolic signatures were identified. Particularly, the body mass index (BMI)-associated metabolic component was positively related to glutamic acid, tyrosine, PC aaC38:3, and liver function score and negatively to lysoPC aC17:0 and aC18:2. The lifetime alcohol-specific signature had negative loadings on sphingomyelins (SM C16:1, C18:1, SM(OH) C14:1, C16:1 and C22:2). Both exposures were associated with increased HCC with total effects (TE) = 1.23 (95% confidence interval = 0.93-1.62) and 1.40 (1.14-1.72), respectively, for BMI and alcohol consumption. Both metabolic signatures mediated the association between BMI and lifetime alcohol consumption and HCC with natural indirect effects, respectively, equal to 1.56 (1.24-1.96) and 1.09 (1.03-1.15), accounting for a proportion mediated of 100% and 24%.

    Conclusions: In a refined MITM framework, relevant metabolic signatures were identified as mediators in the relationship between lifestyle exposures and HCC risk.

    Impact: The understanding of the biological basis for the relationship between modifiable exposures and cancer would pave avenues for clinical and public health interventions on metabolic mediators.

  • 67. Baba, Kerstin
    et al.
    Fransson, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lindh, Jack
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Use of a modified ESAS in cancer patients: a pilot study of patient and staff experiences2007In: International Journal of Palliative Nursing, ISSN 1357-6321, E-ISSN 2052-286X, Vol. 13, no 12, p. 610-616Article in journal (Refereed)
    Abstract [en]

    Aim: To evaluate the feasibility of a modified Edmonton Symptom Assessment Scale (ESAS) for monitoring symptoms in oncological palliative care.

    Methods: A modified ESAS was delivered daily to 28 patients with advanced cancer. A questionnaire to discover staff members’ opinions on the ESAS was delivered at the end of the study. Structured interviews were used to examine patients’ opinions on the ESAS.

    Results: The mean total ESAS score was 28.9 on inclusion day and 25.8 on Day 3 (p=0.531). Eleven of 21 of the staff considered the ESAS to be a ‘good’ or ‘very good’ way to obtain information about patients’ symptoms. Seventeen of 24 patients who participated in the interview felt that ESAS was easy to fill in, and that there were no missing questions.

    Conclusion: The patients felt that the modified ESAS contained relevant symptoms, and that the questionnaires were easy to fill in. The staff considered the modified ESAS to be a useful instrument for obtaining information about patients’ symptom distress. The modified ESAS is a good instrument for use as part of the daily clinical routine, as well as for monitoring symptoms in palliative oncological care.

  • 68. Bailey-Wilson, Joan E
    et al.
    Childs, Erica J
    Cropp, Cheryl D
    Schaid, Daniel J
    Xu, Jianfeng
    Camp, Nicola J
    Cannon-Albright, Lisa A
    Farnham, James M
    George, Asha
    Powell, Isaac
    Carpten, John D
    Giles, Graham G
    Hopper, John L
    Severi, Gianluca
    English, Dallas R
    Foulkes, William D
    Maehle, Lovise
    Moller, Pal
    Eeles, Rosalind
    Easton, Douglas
    Guy, Michelle
    Edwards, Steve
    Badzioch, Michael D
    Whittemore, Alice S
    Oakley-Girvan, Ingrid
    Hsieh, Chih-Lin
    Dimitrov, Latchezar
    Stanford, Janet L
    Karyadi, Danielle M
    Deutsch, Kerry
    McIntosh, Laura
    Ostrander, Elaine A
    Wiley, Kathleen E
    Isaacs, Sarah D
    Walsh, Patrick C
    Thibodeau, Stephen N
    McDonnell, Shannon K
    Hebbring, Scott
    Lange, Ethan M
    Cooney, Kathleen A
    Tammela, Teuvo LJ
    Schleutker, Johanna
    Maier, Christiane
    Bochum, Sylvia
    Hoegel, Josef
    Gronberg, Henrik
    Wiklund, Fredrik
    Emanuelsson, Monica
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Cancel-Tassin, Geraldine
    Valeri, Antoine
    Cussenot, Olivier
    Isaacs, William B
    Analysis of Xq27-28 linkage in the international consortium for prostate cancer genetics (ICPCG) families2012In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 13, p. 46-Article in journal (Refereed)
    Abstract [en]

    Background: Genetic variants are likely to contribute to a portion of prostate cancer risk. Full elucidation of the genetic etiology of prostate cancer is difficult because of incomplete penetrance and genetic and phenotypic heterogeneity. Current evidence suggests that genetic linkage to prostate cancer has been found on several chromosomes including the X; however, identification of causative genes has been elusive.

    Methods: Parametric and non-parametric linkage analyses were performed using 26 microsatellite markers in each of 11 groups of multiple-case prostate cancer families from the International Consortium for Prostate Cancer Genetics (ICPCG). Meta-analyses of the resultant family-specific linkage statistics across the entire 1,323 families and in several predefined subsets were then performed.

    Results: Meta-analyses of linkage statistics resulted in a maximum parametric heterogeneity lod score (HLOD) of 1.28, and an allele-sharing lod score (LOD) of 2.0 in favor of linkage to Xq27-q28 at 138 cM. In subset analyses, families with average age at onset less than 65 years exhibited a maximum HLOD of 1.8 (at 138 cM) versus a maximum regional HLOD of only 0.32 in families with average age at onset of 65 years or older. Surprisingly, the subset of families with only 2-3 affected men and some evidence of male-to-male transmission of prostate cancer gave the strongest evidence of linkage to the region (HLOD = 3.24, 134 cM). For this subset, the HLOD was slightly increased (HLOD = 3.47 at 134 cM) when families used in the original published report of linkage to Xq27-28 were excluded.

    Conclusions: Although there was not strong support for linkage to the Xq27-28 region in the complete set of families, the subset of families with earlier age at onset exhibited more evidence of linkage than families with later onset of disease. A subset of families with 2-3 affected individuals and with some evidence of male to male disease transmission showed stronger linkage signals. Our results suggest that the genetic basis for prostate cancer in our families is much more complex than a single susceptibility locus on the X chromosome, and that future explorations of the Xq27-28 region should focus on the subset of families identified here with the strongest evidence of linkage to this region.

  • 69. Bainbridge, Matthew N
    et al.
    Armstrong, Georgina N
    Gramatges, M Monica
    Bertuch, Alison A
    Jhangiani, Shalini N
    Doddapaneni, Harsha
    Lewis, Lora
    Tombrello, Joseph
    Tsavachidis, Spyros
    Liu, Yanhong
    Jalali, Ali
    Plon, Sharon E
    Lau, Ching C
    Parsons, Donald W
    Claus, Elizabeth B
    Barnholtz-Sloan, Jill
    Il'yasova, Dora
    Schildkraut, Joellen
    Ali-Osman, Francis
    Sadetzki, Siegal
    Johansen, Christoffer
    Houlston, Richard S
    Jenkins, Robert B
    Lachance, Daniel
    Olson, Sara H
    Bernstein, Jonine L.
    Merrell, Ryan T
    Wrensch, Margaret R
    Walsh, Kyle M
    Davis, Faith G
    Lai, Rose
    Shete, Sanjay
    Aldape, Kenneth
    Amos, Christopher I
    Thompson, Patricia A
    Muzny, Donna M
    Gibbs, Richard A
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa L
    Germline mutations in shelterin complex genes are associated with familial glioma2015In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 107, no 1, article id dju384Article in journal (Refereed)
    Abstract [en]

    Gliomas are the most common brain tumor, with several histological subtypes of various malignancy grade. The genetic contribution to familial glioma is not well understood. Using whole exome sequencing of 90 individuals from 55 families, we identified two families with mutations in POT1 (p.G95C, p.E450X), a member of the telomere shelterin complex, shared by both affected individuals in each family and predicted to impact DNA binding and TPP1 binding, respectively. Validation in a separate cohort of 264 individuals from 246 families identified an additional mutation in POT1 (p.D617Efs), also predicted to disrupt TPP1 binding. All families with POT1 mutations had affected members with oligodendroglioma, a specific subtype of glioma more sensitive to irradiation. These findings are important for understanding the origin of glioma and could have importance for the future diagnostics and treatment of glioma.

  • 70. Baltar, Valéria Troncoso
    et al.
    Xun, Wei W
    Chuang, Shu-Chun
    Relton, Caroline
    Ueland, Per Magne
    Vollset, Stein Emil
    Midttun, Øivind
    Johansson, Mattias
    Slimani, Nadia
    Jenab, Mazda
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Kaaks, Rudolf
    Rohrmann, Sabine
    Boeing, Heiner
    Weikert, Cornelia
    Bueno-de-Mesquita, H Bas
    Boshuizen, Hendriek C
    van Gils, Carla H
    Peeters, Petra H M
    Agudo, Antonio
    Barricarte, Aurelio
    Navarro, Carmen
    Rodríguez, Laudina
    Castaño, José Maria Huerta
    Larrañaga, Nerea
    Pérez, Maria José Sánchez
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E
    Crowe, Francesca
    Gallo, Valentina
    Norat, Teresa
    Tagliabue, Giovanna
    Masala, Giovanna
    Panico, Salvatore
    Sacerdote, Carlota
    Tumino, Rosario
    Trichopoulou, Antonia
    Lagiou, Pagona
    Bamia, Christina
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Roswall, Nina
    Tjønneland, Anne
    Riboli, Elio
    Brennan, Paul
    Vineis, Paolo
    Smoking, secondhand smoke, and cotinine levels in a subset of EPIC cohort2011In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 20, no 5, p. 869-875Article in journal (Refereed)
    Abstract [en]

    Background: Several countries are discussing new legislation regarding the ban on smoking in public places, based on the growing evidence of the hazards of secondhand smoke (SHS) exposure. The objective of the present study is to quantitatively assess the relationship between smoking, SHS, and serum cotinine levels in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    Methods: From a study on lung cancer in the EPIC cohort, questionnaire information on smoking was collected at enrolment, and cotinine was measured in serum. Three statistical models were applied by using samples available in a cross-section design: (i) cotinine levels by categories combining smoking and SHS (n = 859); (ii) the effect of hours of passive smoking exposure in nonsmokers only (n = 107); (iii) the effect of the number of cigarettes consumed per day in current smokers only (n = 832). All models were adjusted for country, sex, age, and body mass index.

    Results: Among nonsmokers, passive smokers presented significant differences in cotinine compared with nonexposed, with a marked (but not significant) difference among former-smokers. A one hour per day increment of SHS gave rise to a significant 2.58 nmol/L (0.45 ng/mL) increase in mean serum cotinine (P < 0.001). In current smokers, a one cigarette per day increment gave rise to a significant 22.44 nmol/L (3.95 ng/mL) increase in cotinine mean (P < 0.001).

    Conclusions: There is clear evidence that not only tobacco smoking but also involuntary exposure increases cotinine levels.

    Impact: This study strengthens the evidence for the benefits of a smoking ban in public places.

  • 71. Baltar, Valéria Troncoso
    et al.
    Xun, Wei W
    Johansson, Mattias
    International Agency for Research on Cancer, Lyon, France.
    Ferrari, Pietro
    Chuang, Shu-Chun
    Relton, Caroline
    Ueland, Per Magne
    Midttun, Oivind
    Slimani, Nadia
    Jenab, Mazda
    Clavel-Chapelon, Françoise
    Boutron-Ruault, Marie-Christine
    Fagherazzi, Guy
    Kaaks, Rudolf
    Rohrmann, Sabine
    Boeing, Heiner
    Weikert, Cornelia
    Bueno-de-Mesquita, Bas
    Boshuizen, Hendriek
    van Gils, Carla H
    Onland-Moret, N Charlotte
    Agudo, Antonio
    Barricarte, Aurelio
    Navarro, Carmen
    Rodríguez, Laudina
    Castaño, José Maria Huerta
    Larrañaga, Nerea
    Khaw, Kay-Tee
    Wareham, Nick
    Allen, Naomi E
    Crowe, Francesca
    Gallo, Valentina
    Norat, Teresa
    Krogh, Vittorio
    Masala, Giovanna
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Trichopoulou, Antonia
    Lagiou, Pagona
    Trichopoulos, Dimitrios
    Rasmuson, Torgny
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Biobank Research. Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Roswall, Nina
    Tjønneland, Anne
    Riboli, Elio
    Brennan, Paul
    Vineis, Paolo
    A structural equation modelling approach to explore the role of B vitamins and immune markers in lung cancer risk2013In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 28, no 8, p. 677-688Article in journal (Refereed)
    Abstract [en]

    The one-carbon metabolism (OCM) is considered key in maintaining DNA integrity and regulating gene expression, and may be involved in the process of carcinogenesis. Several B-vitamins and amino acids have been implicated in lung cancer risk, via the OCM directly as well as immune system activation. However it is unclear whether these factors act independently or through complex mechanisms. The current study applies structural equations modelling (SEM) to further disentangle the mechanisms involved in lung carcinogenesis. SEM allows simultaneous estimation of linear relations where a variable can be the outcome in one equation and the predictor in another, as well as allowing estimation using latent variables (factors estimated by correlation matrix). A large number of biomarkers have been analysed from 891 lung cancer cases and 1,747 controls nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Four putative mechanisms in the OCM and immunity were investigated in relation to lung cancer risk: methionine-homocysteine metabolism, folate cycle, transsulfuration, and mechanisms involved in inflammation and immune activation, all adjusted for tobacco exposure. The hypothesized SEM model confirmed a direct and protective effect for factors representing methionine-homocysteine metabolism (p = 0.020) and immune activation (p = 0.021), and an indirect protective effect of folate cycle (p = 0.019), after adjustment for tobacco smoking. In conclusion, our results show that in the investigation of the involvement of the OCM, the folate cycle and immune system in lung carcinogenesis, it is important to consider complex pathways (by applying SEM) rather than the effects of single vitamins or nutrients (e.g. using traditional multiple regression). In our study SEM were able to suggest a greater role of the methionine-homocysteine metabolism and immune activation over other potential mechanisms.

  • 72. Bamia, Christina
    et al.
    Lagiou, Pagona
    Buckland, Genevieve
    Grioni, Sara
    Agnoli, Claudia
    Taylor, Aliki J.
    Dahm, Christina C.
    Overvad, Kim
    Olsen, Anja
    Tjonneland, Anne
    Cottet, Vanessa
    Boutron-Ruault, Marie-Christine
    Morois, Sophie
    Grote, Verena
    Teucher, Birgit
    Boeing, Heiner
    Buijsse, Brian
    Trichopoulos, Dimitrios
    Adarakis, George
    Tumino, Rosario
    Naccarati, Alessio
    Panico, Salvatore
    Palli, Domenico
    Bueno-de-Mesquita, H. Bas
    van Duijnhoven, Fraenzel J. B.
    Peeters, Petra H. M.
    Engeset, Dagrun
    Skeie, Guri
    Lund, Eiliv
    Sanchez, Maria-Jose
    Barricarte, Aurelio
    Huerta, Jose-Maria
    Ramon Quiros, J.
    Dorronsoro, Miren
    Ljuslinder, Ingrid
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Palmqvist, Richard
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Drake, Isabel
    Key, Timothy J.
    Khaw, Kay-Tee
    Wareham, Nick
    Romieu, Isabelle
    Fedirko, Veronika
    Jenab, Mazda
    Romaguera, Dora
    Norat, Teresa
    Trichopoulou, Antonia
    Mediterranean diet and colorectal cancer risk: results from a European cohort2013In: European Journal of Epidemiology, ISSN 0393-2990, E-ISSN 1573-7284, Vol. 28, no 4, p. 317-328Article in journal (Refereed)
    Abstract [en]

    The authors investigated the association of adherence to Mediterranean diet with colorectal cancer (CRC) risk in the European Prospective Investigation into Cancer and nutrition study. Adherence to Mediterranean diet was expressed through two 10-unit scales, the Modified Mediterranean diet score (MMDS) and the Centre-Specific MMDS (CSMMDS). Both scales share the same dietary components but differ in the cut-off values that were used for these components in the construction of the scales. Adjusted hazard ratios (HR) for the associations of these scales with CRC incidence were estimated. After 5,296,617 person-years of follow-up, 4,355 incident CRC cases were identified. A decreased risk of CRC, of 8 and 11 % was estimated when comparing the highest (scores 6-9) with the lowest (scores 0-3) adherence to CSMMDS and MMDS respectively. For MMDS the HR was 0.89 (95 % confidence interval (CI): 0.80, 0.99). A 2-unit increment in either Mediterranean scale was associated with a borderline statistically significant 3 to 4 % reduction in CRC risk (HR for MMDS: 0.96; 95 % CI: 0.92, 1.00). These associations were somewhat more evident, among women, were mainly manifested for colon cancer risk and their magnitude was not altered when alcohol was excluded from MMDS. These findings suggest that following a Mediterranean diet may have a modest beneficial effect on CRC risk.

  • 73. Barekati, Zeinab
    et al.
    Radpour, Ramin
    Kohler, Corina
    Zhang, Bei
    Toniolo, Paolo
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lv, Qing
    Zheng, Hong
    Zhong, Xiao Yan
    Methylation profile of TP53 regulatory pathway and mtDNA alterations in breast cancer patients lacking TP53 mutations2010In: Human Molecular Genetics, ISSN 0964-6906, E-ISSN 1460-2083, Vol. 19, no 15, p. 2936-2946Article in journal (Refereed)
    Abstract [en]

    The present study investigated promoter hypermethylation of TP53 regulatory pathways providing a potential link between epigenetic changes and mitochondrial DNA (mtDNA) alterations in breast cancer patients lacking a TP53 mutation. The possibility of using the cancer-specific alterations in serum samples as a blood-based test was also explored. Triple-matched samples (cancerous tissues, matched adjacent normal tissues and serum samples) from breast cancer patients were screened for TP53 mutations, and the promoter methylation profile of P14(ARF), MDM2, TP53 and PTEN genes was analyzed as well as mtDNA alterations, including D-loop mutations and mtDNA content. In the studied cohort, no mutation was found in TP53 (DNA-binding domain). Comparison of P14(ARF) and PTEN methylation patterns showed significant hypermethylation levels in tumor tissues (P < 0.05 and <0.01, respectively) whereas the TP53 tumor suppressor gene was not hypermethylated (P < 0.511). The proportion of PTEN methylation was significantly higher in serum than in the normal tissues and it has a significant correlation to tumor tissues (P < 0.05). mtDNA analysis revealed 36.36% somatic and 90.91% germline mutations in the D-loop region and also significant mtDNA depletion in tumor tissues (P < 0.01). In addition, the mtDNA content in matched serum was significantly lower than in the normal tissues (P < 0.05). These data can provide an insight into the management of a therapeutic approach based on the reversal of epigenetic silencing of the crucial genes involved in regulatory pathways of the tumor suppressor TP53. Additionally, release of significant aberrant methylated PTEN in matched serum samples might represent a promising biomarker for breast cancer.

  • 74. Barekati, Zeinab
    et al.
    Radpour, Ramin
    Lu, Qing
    Bitzer, Johannes
    Zheng, Hong
    Toniolo, Paolo
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Zhong, Xiao Yan
    Methylation signature of lymph node metastases in breast cancer patients2012In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 12, p. 244-Article in journal (Refereed)
    Abstract [en]

    Background: Invasion and metastasis are two important hallmarks of malignant tumors caused by complex genetic and epigenetic alterations. The present study investigated the contribution of aberrant methylation profiles of cancer related genes, APC, BIN1, BMP6, BRCA1, CST6, ESR-b, GSTP1, P14 (ARF), P16 (CDKN2A), P21 (CDKN1A), PTEN, and TIMP3, in the matched axillary lymph node metastasis in comparison to the primary tumor tissue and the adjacent normal tissue from the same breast cancer patients to identify the potential of candidate genes methylation as metastatic markers. Methods: The quantitative methylation analysis was performed using the SEQUENOM's EpiTYPER (TM) assay which relies on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results: The quantitative DNA methylation analysis of the candidate genes showed higher methylation proportion in the primary tumor tissue than that of the matched normal tissue and the differences were significant for the APC, BIN1, BMP6, BRCA1, CST6, ESR-b, P16, PTEN and TIMP3 promoter regions (P<0.05). Among those candidate methylated genes, APC, BMP6, BRCA1 and P16 displayed higher methylation proportion in the matched lymph node metastasis than that found in the normal tissue (P<0.05). The pathway analysis revealed that BMP6, BRCA1 and P16 have a role in prevention of neoplasm metastasis. Conclusions: The results of the present study showed methylation heterogeneity between primary tumors and metastatic lesion. The contribution of aberrant methylation alterations of BMP6, BRCA1 and P16 genes in lymph node metastasis might provide a further clue to establish useful biomarkers for screening metastasis.

  • 75. Bartek, Jiri, Jr.
    et al.
    Förander, Petter
    Thurin, Erik
    Wangerid, Theresa
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre Stockholm/Gotland, Stockholm, Sweden.
    Hesselager, Göran
    Jakola, Asgeir Store
    Short-Term Surgical Outcome for Vestibular Schwannoma in Sweden: A Nation-Wide Registry Study2019In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 10, article id 43Article in journal (Refereed)
    Abstract [en]

    Background: Vestibular Schwannoma (VS) is a benign neoplasm arising from the 8th cranial nerve, with surgery one of the treatment modalities. In a nation-wide registry study, we describe the baseline, treatment characteristics, and short-term outcome in patients surgically treated for VS.

    Methods: We performed a nationwide study with data from the Swedish Brain Tumor Registry (SBTR) for all adults diagnosed with VS 2009–2015. Patient symptoms, tumor characteristics, and postoperative complications were analyzed.

    Results: In total 348 patients underwent surgery for VS. Mean age was 50.6 ± 14.5 years and 165 patients (47.4%) were female. The most common symptom was focal neurological deficit (92.0%), with only 25 (7.2%) being asymptomatic prior to surgery, and 217 (63.6%) had no restriction in activity. Following surgery, 100 (28.7%) patients developed new deficit(s). In terms of postoperative complications; 11 (3.2%) had a hematoma, 35 (10.1%) an infection, 10 (2.9%) a venous thromboembolism, and 23 (6.6%) had a reoperation due to complication. There were no deaths within 30-days after surgery. When grouped according to tumor size (< 4 vs. ≥4 cm), those with ≥4 cm tumors were more often males (p = 0.02), had more often ICP related symptoms (p = 0.03) and shorter time from imaging to surgery (p < 0.01). Analysis of the younger (< 65 years) vs. elderly (≥65 years) revealed no difference in outcome except increased 1-year mortality (p = 0.002) in elderly.

    Conclusion: In this nation-wide registry-study, we benchmark the 30-day complication rate after VS surgery as collected by the SBTR. Further, we present the current neurosurgical outcome data from both VS smaller than 40 mm compared to larger tumors, as well as younger vs. elderly VS patients. Since surgical decision making is a careful consideration of short term risk vs. long term benefit, this information can be useful in clinical decision making.

  • 76. Barton, Maria
    et al.
    Santucci-Pereira, Julia
    de Cicco, Ricardo Lopez
    Russo, Irma H.
    Ross, Eric A.
    Slifker, Michael
    Peri, Suraj
    Bordas, Pal
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research. Umeå University, Faculty of Medicine, Department of Biobank Research.
    Toniolo, Paolo
    Russo, Jose
    Long noncoding RNAs in the postmenopausal breast and their role in cancer prevention2014In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 19Article in journal (Other academic)
  • 77. Belitskaya-Lévy, Ilana
    et al.
    Zeleniuch-Jacquotte, Anne
    Russo, Jose
    Russo, Irma H
    Bordás, Pal
    Ahman, Janet
    Afanasyeva, Yelena
    Johansson, Robert
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Lenner, Per
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Li, Xiaochun
    de Cicco, Ricardo López
    Peri, Suraj
    Ross, Eric
    Russo, Patricia A
    Santucci-Pereira, Julia
    Sheriff, Fathima S
    Slifker, Michael
    Hallmans, Göran
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Nutritional Research.
    Toniolo, Paolo
    Arslan, Alan A
    Characterization of a genomic signature of pregnancy identified in the breast2011In: Cancer Prevention Research, ISSN 1940-6207, E-ISSN 1940-6215, Vol. 4, no 9, p. 1457-1464Article in journal (Refereed)
    Abstract [en]

    The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer.

  • 78. Bengtsson, Daniel
    et al.
    Joost, Patrick
    Aravidis, Christos
    Stenmark, Marie Askmalm
    Backman, Ann-Sofie
    Melin, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    von Salome, Jenny
    Zagoras, Theofanis
    Gebre-Medhin, Samuel
    Burman, Pia
    Corticotroph Pituitary Carcinoma in a Patient With Lynch Syndrome (LS) and Pituitary Tumors in a Nationwide LS Cohort2017In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 102, no 11, p. 3928-3932Article in journal (Refereed)
    Abstract [en]

    Context: Lynch syndrome (LS) is a cancer-predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported.

    Case: A 51-year-old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patient’s germline mutation and displayed defect MMR function. Sixteen months later, the tumor had developed into a carcinoma with widespread liver metastases. The patient prompted us to perform a nationwide study in LS.

    Nationwide Study: A diagnosis consistent with a pituitary tumor was sought for in the Swedish National Patient Registry. In 910 patients with LS, representing all known cases in Sweden, another two clinically relevant pituitary tumors were found: an invasive nonsecreting macroadenoma and a microprolactinoma (i.e., in total three tumors vs. one expected).

    Conclusion: Germline mutations in MMR genes may contribute to the development and/or the clinical course of pituitary tumors. Because tumors with MMR mutations are susceptible to treatment with immune checkpoint inhibitors, we suggest to actively ask for a family history of LS in the workup of patients with aggressive pituitary tumors.

  • 79.
    Bengtsson Ågren, Elsa
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Rehabilitation needs before, during and after adjuvant chemotherapy2017Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
  • 80.
    Bergdahl, Ingvar A
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Jonsson, Håkan
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Eriksson, Kåre
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Damber, Lena
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Järvholm, Bengt
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    Lung cancer and exposure to quartz and diesel exhaust in Swedish iron ore miners with concurrent exposure to radon2010In: Occupational and Environmental Medicine, ISSN 1351-0711, E-ISSN 1470-7926, Vol. 67, no 8, p. 513-518Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES: Studies of underground miners have documented an increased risk of lung cancer mainly linked to radon exposure but possibly influenced by other concurrent exposures. METHODS: A cohort study was carried out in 8321 iron ore miners with low exposure to radon, employed in 1923-1998 and followed up for lung cancer in 1958-2000. Historical exposures to radon, crystalline silica and diesel exhaust were assessed. Data including exposure to radon, quartz and diesel exhaust from another mine with higher exposure to radon were reanalysed. RESULTS: Miners had increased risk for lung cancer (SIR 1.48 (95% CI 1.22 to 1.78), based on 112 cases during 227,000 person-years). The increased risk could not be explained by exposure to radon or diesel exhaust but was associated with exposure to crystalline silica: SIR 0.96 (0.53 to 1.62), 1.45 (1.10 to 1.87), 1.99 (1.31 to 2.90) and 1.77 (0.92 to 3.10) in groups with exposure to 0, 0-2, 2-5 and >5 mg years/m3, respectively. Reanalysis of data from the other mine indicated that quartz was a possible confounder in the analysis of relationship between radon and lung cancer. In the highest radon exposed group, the point estimate for the RR decreased from 5.65 to 3.90 when adjusting for concurrent exposure to quartz. CONCLUSIONS: Crystalline silica, a known carcinogen, probably affects lung cancer risk in iron ore miners. The main implication of the results is for interpretation of the dose-response curve for radon and lung cancer in underground iron ore miners. Since exposure to radon and quartz is often correlated, quartz exposure can be an important confounder.

  • 81.
    Bergenheim, A Tommy
    et al.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Capala, Jacek
    Roslin, Michael
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Distribution of BPA and metabolic assessment in glioblastoma patients during BNCT treatment: a microdialysis study2005In: J Neurooncol, ISSN 0167-594X, Vol. 71, no 3, p. 287-293Article in journal (Refereed)
  • 82.
    Bergenheim, A Tommy
    et al.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Roslin, Michael
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Ungerstedt, Urban
    Waldenström, Anders
    Umeå University, Faculty of Medicine, Public Health and Clinical Medicine, Medicine.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Ronquist, Gunnar
    Metabolic manipulation of glioblastoma in vivo by retrograde microdialysis of L-2, 4 diaminobutyric acid (DAB).2006In: J Neurooncol, ISSN 0167-594X, Vol. 80, no 3, p. 285-293Article in journal (Refereed)
  • 83.
    Bergenheim, Tommy
    et al.
    Umeå University, Faculty of Medicine, Pharmacology and Clinical Neuroscience, Neurosurgery.
    Malmström, Annika
    Bolander, Hans
    Michanek, Annika
    Stragliotto, Giuseppe
    Damber, Lena
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Björ, Ove
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Registrering av primära hjärntumörer mått på nationell vårdkvalitet. Regionala skillnader avslöjade.2007In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 104, no 5, p. 332-341Article in journal (Refereed)
  • 84. Berger, Eloise
    et al.
    Delpierre, Cyrille
    Hosnijeh, Fatemeh Saberi
    Kelly-Irving, Michelle
    Portengen, Lutzen
    Bergdahl, Ingvar
    Umeå University, Faculty of Medicine, Department of Biobank Research.
    Johansson, Ann Sofie
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Krogh, Vittorio
    Palli, Domenico
    Panico, Salvatore
    Sacerdote, Carlotta
    Tumino, Rosario
    Kyrtopoulos, Soterios A.
    Vineis, Paolo
    Chadeau-Hyam, Marc
    Vermeulen, Roel
    Castagné, Raphaële
    Association between low-grade inflammation and Breast cancer and B-cell Myeloma and Non-Hodgkin Lymphoma: findings from two prospective cohorts2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 10805Article in journal (Refereed)
    Abstract [en]

    Chronic inflammation may be involved in cancer development and progression. Using 28 inflammatory-related proteins collected from prospective blood samples from two case-control studies nested in the Italian component of the European Prospective Investigation into Cancer and nutrition (n = 261) and in the Northern Sweden Health and Disease Study (n = 402), we tested the hypothesis that an inflammatory score is associated with breast cancer (BC) and.-cell Non-Hodgkin Lymphoma (B-cell NHL, including 68 multiple myeloma cases) onset. We modelled the relationship between this inflammatory score and the two cancers studied: (BC and B-cell NHL) using generalised linear models, and assessed, through adjustments the role of behaviours and lifestyle factors. Analyses were performed by cancer types pooling both populations, and stratified by cohorts, and time to diagnosis. Our results suggested a lower inflammatory score in B-cell NHL cases (β = -1.28, p = 0.012), and, to lesser, extent with BC (β= -0.96, p = 0.33) compared to controls, mainly driven by cancer cases diagnosed less than 6 years after enrolment. These associations were not affected by subsequent adjustments for potential intermediate confounders, notably behaviours. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated. These observations call for further studies involving larger populations, larger variety of cancer types and repeated measures of larger panel of inflammatory markers.

  • 85.
    Bergh, Johanna
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology. Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Marklund, Ingrid
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Gustavsson, C
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Wiklund, Fredrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Allard, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology.
    Alexeyev, Olog
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology, Virology. Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    No link between viral findings in the prostate and subsequent cancer development2007In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 96, no 1, p. 137-139Article in journal (Refereed)
    Abstract [en]

    In an investigation of 201 prostate tissue samples from patients with benign prostate hyperplasia that later progressed to prostate cancer and 201 matched controls that did not, there were no differences in the prevalence of adenovirus, herpesvirus, papilloma virus, polyoma virus and Candida albicans DNA.

  • 86.
    Bergh, Johanna
    et al.
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Marklund, Ingrid
    Umeå University, Faculty of Medicine, Clinical Microbiology, Virology.
    Thellenberg-Karlsson, Camilla
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Grönberg, Henrik
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Elgh, Fredrik
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Alexeyev, Oleg A
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Detection of Escherichia coli 16S RNA and Cytotoxic Necrotizing Factor 1 Gene in Benign Prostate Hyperplasia.2007In: Eur Urol, ISSN 0302-2838, Vol. 51, no 2, p. 457-463Article in journal (Refereed)
  • 87. Bergh, Jonas
    et al.
    Jönsson, Per-Ebbe
    Lidbrink, Elisabet Kerstin
    Trudeau, Maureen
    Eiermann, Wolfgang
    Brattström, Daniel
    Lindemann, Justin P O
    Wiklund, Fredrik
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    FACT: An Open-Label Randomized Phase III Study of Fulvestrant and Anastrozole in Combination Compared With Anastrozole Alone as First-Line Therapy for Patients With Receptor-Positive Postmenopausal Breast Cancer2012In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 30, no 16, p. 1919-1925Article in journal (Refereed)
    Abstract [en]

    Purpose: To compare the effect of therapy with anastrozole versus a combination of fulvestrant and anastrozole in women in first relapse of endocrine-responsive breast cancer.

    Patients and Methods: Postmenopausal women, or premenopausal women receiving a gonadotropin-releasing hormone agonist, with estrogen receptor– and/or progesterone receptor–positive disease at first relapse after primary treatment of localized disease were open-label randomly assigned to a fulvestrant loading dose (LD) regimen followed by monthly injection plus 1 mg of anastrozole daily or to 1 mg of anastrozole daily alone. The primary end point was time to progression (TTP).

    Results: In all, 514 women were randomly assigned to fulvestrant plus anastrozole (experimental arm; n = 258) or anastrozole (standard arm; n = 256). Approximately two thirds had received adjuvant antiestrogens, but only eight individuals had received an aromatase inhibitor. Median TTP was 10.8 and 10.2 months in the experimental versus standard arm, respectively (hazard ratio [HR] = 0.99; 95% CI, 0.81 to 1.20; P = .91); median overall survival was 37.8 and 38.2 months, respectively (HR = 1.0; 95% CI, 0.76 to 1.32; P = 1.00). Incidences of prespecified adverse events (AEs) were similar. Hot flashes were more common in the experimental arm: 63 patients (24.6%) versus 35 patients (13.8%) in the standard arm (P = .0023). Death owing to AEs was reported in 11 (4.3%) and five patients (2.0%) in the experimental versus standard arm, respectively.

    Conclusion: Fulvestrant (250 mg + LD regimen) in combination with anastrozole offered no clinical efficacy advantage over anastrozole monotherapy in this population of individuals with a relatively high proportion of previous adjuvant antiestrogen exposure.

  • 88. Berglund, Mattias
    et al.
    Enblad, Gunilla
    Thunberg, Ulf
    Amini, Rose-Marie
    Sundström, Christer
    Roos, Göran
    Umeå University, Faculty of Medicine, Medical Biosciences, Pathology.
    Erlanson, Martin
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Rosenquist, Richard
    Larsson, Catharina
    Lagercrantz, Svetlana
    Genomic imbalances during transformation from follicular lymphoma to diffuse large B-cell lymphoma.2007In: Modern Patholology, ISSN 0893-3952, Vol. 20, no 1, p. 63-75Article in journal (Refereed)
  • 89. Bergman, Annika
    et al.
    Sahlin, Pelle
    Emanuelsson, Monica
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Carén, Helena
    Tarnow, Peter
    Martinsson, Tommy
    Grönberg, Henrik
    Stenman, Göran
    Germline mutation screening of the Saethre-Chotzen-associated genes TWIST1 and FGFR3 in families with BRCA1/2-negative breast cancer.2009In: Scandinavian journal of plastic and reconstructive surgery and hand surgery / Nordisk plastikkirurgisk forening [and] Nordisk klubb for handkirurgi, ISSN 1651-2073, Vol. 43, no 5, p. 251-255Article in journal (Refereed)
    Abstract [en]

    Saethre-Chotzen syndrome is one of the most common craniosynostosis syndromes. It is an autosomal dominantly inherited disorder with variable expression that is caused by germline mutations in the TWIST1 gene or more rarely in the FGFR2 or FGFR3 genes. We have previously reported that patients with Saethre-Chotzen syndrome have an increased risk of developing breast cancer. Here we have analysed a cohort of 26 women with BRCA1/2-negative hereditary breast cancer to study whether a proportion of these families might have mutations in Saethre-Chotzen-associated genes. DNA sequence analysis of TWIST1 showed no pathogenic mutations in the coding sequence in any of the 26 patients. MLPA (multiplex ligation-dependent probe amplification)-analysis also showed no alterations in copy numbers in any of the craniofacial disorder genes MSX2, ALX4, RUNX2, EFNB1, TWIST1, FGFR1, FGFR2,FGFR3, or FGFR4. Taken together, our findings indicate that mutations in Saethre-Chotzen-associated genes are uncommon or absent in BRCA1/2-negative patients with hereditary breast cancer.

  • 90. Bergqvist, Jenny
    et al.
    Iderberg, Hanna
    Mesterton, Johan
    Bengtsson, Nils
    Wettermark, Bjorn
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre Stockholm-Gotland, Stockholm County Council, Stockholm, Sweden.
    Healthcare resource use, comorbidity, treatment and clinical outcomes for patients with primary intracranial tumors: a Swedish population-based register study2017In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 56, no 3, p. 405-414Article in journal (Refereed)
    Abstract [en]

    Background: Primary intracranial tumors are relatively uncommon and heterogeneous, which make them challenging to study. We coupled data from unique Swedish population-based registries in order to deeper analyze the most common intracranical tumor types. Patient characteristics (e.g. comorbidities), care process measures like adherence to national guidelines, healthcare resource use and clinical outcome was evaluated.

    Materials and methods: A register-based study including several population-based registries for all patients living in Stockholm-Gotland, diagnosed with primary intracranial tumor between 2001 and 2013 was performed. Patient characteristics were captured and investigated in relation to survival, healthcare resource use (inpatient-, outpatient- and primary care) and treatment process.

    Results: High-grade glioma and meningioma were the most common tumor types and most patients (76%) were above the age of 40 in the patient population (n = 3664). Older age, comorbidity (Elixhauser comorbidity index) and type of tumor (high-grade glioma) were associated with lower survival rate and increased use of healthcare resources, analyzed for patients living in Stockholm (n = 3031). The analyses of healthcare use and survival showed no differences between males and females, when stratifying by tumor types. Healthcare processes were not always consistent with existing national treatment recommendations for patients with high-grade gliomas (n = 474) with regard to specified lead times, analyzed in the Swedish Brain Tumor Registry, as also observed at the national level.

    Conclusions: Age, comorbidity and high-grade gliomas, but not sex, were associated with decreased survival and increased use of healthcare resources. Fewer patients than aimed for in national guidelines received care according to specified lead times. The analysis of comprehensive population-based register data can be used to improve future care processes and outcomes.

  • 91. Bergqvist, Jenny
    et al.
    Iderberg, Hanna
    Mesterton, Johan
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Regional Cancer Centre Stockholm Gotland, Stockholm County Council, Stockholm, Sweden.
    The effects of clinical and sociodemographic factors on survival, resource use and lead times in patients with high-grade gliomas: a population-based register study2018In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 139, no 3, p. 599-608Article in journal (Refereed)
    Abstract [en]

    Background: Previous studies indicate an effect of sociodemographic factors on risk for being diagnosed with, as well as on survival of cancer in general. Our primary aim was to analyse sociodemographic factors, resource use and lead times in health care after diagnosis with high grade malignant glioma (HGG) in a large population based cohort.

    Methods: A register-based study using several unique high-coverage registries. All patients over the age of 18 diagnosed with HGG in the Swedish Stockholm-Gotland region between 2001 and 2013 (n=1149) were included.

    Results: In multivariable cox proportional hazard model of survival, older age, male sex and high tumour grade were associated with worse survival. No significant differences could be seen related to country of birth. A high disposable income was associated with better survival and fewer occasions of pre-diagnostic inpatient care. Older age and comorbidities were correlated with a significantly increased number of outpatient visits the year before HGG diagnosis. In addition, male sex, being born outside Sweden was associated to a higher number of outpatient visits the year after diagnosis in multivariable analysis. Leadtime from diagnosis (first suspicion on brain scan) to surgery showed that the oldest patients, patients with comorbidity and patients born outside Europe had to wait longer for surgery.

    Conclusions: Sociodemographic factors like education, income and country of birth have impact on care processes both before and after the diagnosis HGG. This needs to be acknowledged in addition to important clinical factors like age, comorbidity and tumour grade, in order to accomplish more equal cancer care.

  • 92. Bergqvist, Michael
    et al.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Radiation Sciences, Oncology.
    Brattström, Daniel
    Novel agents in the treatment of non-small cell lung cancer: implications for neoadjuvant chemotherapy?2005In: In Vivo, ISSN 0258-851X, Vol. 19, no 3, p. 523-533Article in journal (Refereed)
  • 93. Berntsson, Shala G.
    et al.
    Merrell, Ryan T.
    Amirian, E. Susan
    Armstrong, Georgina N.
    Lachance, Daniel
    Smits, Anja
    Zhou, Renke
    Jacobs, Daniel I.
    Wrensch, Margaret R.
    Olson, Sara H.
    Il'yasova, Dora
    Claus, Elizabeth B.
    Barnholtz-Sloan, Jill S.
    Schildkraut, Joellen
    Sadetzki, Siegal
    Johansen, Christoffer
    Houlston, Richard S.
    Jenkins, Robert B.
    Bernstein, Jonine L.
    Lai, Rose
    Shete, Sanjay
    Amos, Christopher I.
    Bondy, Melissa L.
    Melin, Beatrice S.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Glioma-related seizures in relation to histopathological subtypes: a report from the glioma international case-control study2018In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 265, no 6, p. 1432-1442Article in journal (Refereed)
    Abstract [en]

    Background: The purpose of this study was to evaluate the distribution of glioma-related seizures and seizure control at the time of tumor diagnosis with respect to tumor histologic subtypes, tumor treatment and patient characteristics, and to compare seizure history preceding tumor diagnosis (or study enrollment) between glioma patients and healthy controls.

    Methods: The Glioma International Case Control study (GICC) risk factor questionnaire collected information on demographics, past medical/medication history, and occupational history. Cases from eight centers were also asked detailed questions on seizures in relation to glioma diagnosis; cases (n = 4533) and controls (n = 4171) were also asked about seizures less than 2 years from diagnosis and previous seizure history more than 2 years prior to tumor diagnosis, including childhood seizures.

    Results: Low-grade gliomas (LGGs), particularly oligodendrogliomas/oligoastrocytomas, had the highest proportion of glioma-related seizures. Patients with low-grade astrocytoma demonstrated the most medically refractory seizures. A total of 83% of patients were using only one antiepileptic drug (AED), which was levetiracetam in 71% of cases. Gross total resection was strongly associated with reduced seizure frequency (p < 0.009). No significant difference was found between glioma cases and controls in terms of seizure occurring more than 2 years before diagnosis or during childhood.

    Conclusions: Our study showed that glioma-related seizures were most common in low-grade gliomas. Gross total resection was associated with lower seizure frequency. Additionally, having a history of childhood seizures is not a risk factor ***for developing glioma-related seizures or glioma.

  • 94. Berntsson, Shala Ghaderi
    et al.
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Bondy, Melissa
    Qu, Mingqi
    Smits, Anja
    Tumor-associated epilepsy and glioma: Are there common genetic pathways?2009In: Acta oncologica (Stockholm, Sweden), ISSN 1651-226X, Vol. 48, no 7, p. 955-963Article in journal (Refereed)
    Abstract [en]

    Background. Patients with glioma exhibit a great variability in clinical symptoms apart from variations in response to therapy and survival. Many patients present with epileptic seizures at disease onset, especially in case of low-grade gliomas, but not all have seizures. A large proportion of patients develop refractory seizures. It is likely that the variability in epileptic symptoms cannot exclusively be explained by tumor-related factors, but rather reflects complex interaction between tumor-related, environmental and hereditary factors. Material and methods. No data exist on susceptibility genes associated with epileptic symptoms in patients with glioma. However, an increasing number of candidate genes have been proposed for other focal epilepsies such as temporal lobe epilepsy. Some of the susceptibility candidate genes associated with focal epilepsy may contribute to epileptic symptoms also in patients with glioma. Results. This review presents an update on studies on genetic polymorphisms and focal epilepsy and brings forward putative candidate genes for tumor-associated epilepsy, based on the assumption that common etiological pathways may exist for glioma development and glioma-associated seizures. Conclusion. Genes involved in the immune response, in synaptic transmission and in cell cycle control are discussed that may play a role in the pathogenesis of tumor growth as well as epileptic symptoms in patients with gliomas.

  • 95. Berntsson, Shala Ghaderi
    et al.
    Wibom, Carl
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Sjöström, Sara
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Brännström, Thomas
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Broholm, Helle
    Johansson, Christoffer
    Fleming, Sarah J
    McKinney, Patricia A
    Bethke, Lara
    Houlston, Richard
    Smits, Anja
    Andersson, Ulrika
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Melin, Beatrice S
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Analysis of DNA repair gene polymorphisms and survival in low-grade and anaplastic gliomas2011In: Journal of Neuro-Oncology, ISSN 0167-594X, E-ISSN 1573-7373, Vol. 105, no 3, p. 531-538Article in journal (Refereed)
    Abstract [en]

    The purpose of this study was to explore the variation in DNA repair genes in adults with WHO grade II and III gliomas and their relationship to patient survival. We analysed a total of 1,458 tagging single-nucleotide polymorphisms (SNPs) that were selected to cover DNA repair genes, in 81 grade II and grade III gliomas samples, collected in Sweden and Denmark. The statistically significant genetic variants from the first dataset (P < 0.05) were taken forward for confirmation in a second dataset of 72 grade II and III gliomas from northern UK. In this dataset, eight gene variants mapping to five different DNA repair genes (ATM, NEIL1, NEIL2, ERCC6 and RPA4) which were associated with survival. Finally, these eight genetic variants were adjusted for treatment, malignancy grade, patient age and gender, leaving one variant, rs4253079, mapped to ERCC6, with a significant association to survival (OR 0.184, 95% CI 0.054-0.63, P = 0.007). We suggest a possible novel association between rs4253079 and survival in this group of patients with low-grade and anaplastic gliomas that needs confirmation in larger datasets.

  • 96. Best, Myron G.
    et al.
    Sol, Nik
    Kooi, Irsan
    Tannous, Jihane
    Westerman, Bart A.
    Rustenburg, Francois
    Schellen, Pepijn
    Verschueren, Heleen
    Post, Edward
    Koster, Jan
    Ylstra, Bauke
    Ameziane, Najim
    Dorsman, Josephine
    Smit, Egbert F.
    Verheul, Henk M.
    Noske, David P.
    Reijneveld, Jaap C.
    Nilsson, R. Jonas A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Tannous, Bakhos A.
    Wesseling, Pieter
    Wurdinger, Thomas
    RNA-Seq of Tumor-Educated Platelets Enables Blood-Based Pan-Cancer, Multiclass, and Molecular Pathway Cancer Diagnostics2015In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 28, no 5, p. 666-676Article in journal (Refereed)
    Abstract [en]

    Tumor-educated blood platelets (TEPs) are implicated as central players in the systemic and local responses to tumor growth, thereby altering their RNA profile. We determined the diagnostic potential of TEPs by mRNA sequencing of 283 platelet samples. We distinguished 228 patients with localized and metastasized tumors from 55 healthy individuals with 96% accuracy. Across six different tumor types, the location of the primary tumor was correctly identified with 71% accuracy. Also, MET or HER2-positive, and mutant KRAS, EGFR, or PIK3CA tumors were accurately distinguished using surrogate TEP mRNA profiles. Our results indicate that blood platelets provide a valuable platform for pan-cancer, multiclass cancer, and companion diagnostics, possibly enabling clinical advances in blood-based "liquid biopsies".

  • 97. Best, Myron G.
    et al.
    Sol, Nik
    't Veld, Sjors G. J. G. In
    Vancura, Adrienne
    Muller, Mirte
    Niemeijer, Anna-Larissa N.
    Fejes, Aniko V.
    Tjon Kon Fat, Lee-Ann
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    't Veld, Anna E. Huis In
    Leurs, Cyra
    Le Large, Tessa Y.
    Meijer, Laura L.
    Kooi, Irsan E.
    Rustenburg, Francois
    Schellen, Pepijn
    Verschueren, Heleen
    Post, Edward
    Wedekind, Laurine E.
    Bracht, Jillian
    Esenkbrink, Michelle
    Wils, Leon
    Favaro, Francesca
    Schoonhoven, Jilian D.
    Tannous, Jihane
    Meijers-Heijboer, Hanne
    Kazemier, Geert
    Giovannetti, Elisa
    Reijneveld, Jaap C.
    Idema, Sander
    Killestein, Joep
    Heger, Michal
    de Jager, Saskia C.
    Urbanus, Rolf T.
    Hoefer, Imo E.
    Pasterkamp, Gerard
    Mannhalter, Christine
    Gomez-Arroyo, Jose
    Bogaard, Harm-Jan
    Noske, David P.
    Vandertop, W. Peter
    van den Broek, Daan
    Ylstra, Bauke
    Nilsson, Jonas A.
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology. Vrije Univ Amsterdam Med Ctr, Canc Ctr Amsterdam, Dept Neurosurg, De Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands.
    Wesseling, Pieter
    Karachaliou, Niki
    Rosell, Rafael
    Lee-Lewandrowski, Elizabeth
    Lewandrowski, Kent B.
    Tannous, Bakhos A.
    de Langen, Adrianus J.
    Smit, Egbert F.
    van den Heuvel, Michel M.
    Wurdinger, Thomas
    Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets2017In: Cancer Cell, ISSN 1535-6108, E-ISSN 1878-3686, Vol. 32, no 2, p. 238-252Article in journal (Refereed)
    Abstract [en]

    Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.

  • 98.
    Best, Myron
    et al.
    VU Medical Center, Amsterdam, Netherlands.
    Sol, Nik
    VU Medical Center, Amsterdam, Netherlands.
    Kooi, Irsan
    VU Medical Center, Amsterdam, Netherlands.
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Westerman, Bart
    VU Medical Center, Amsterdam, Netherlands.
    Yistra, Bauke
    VU Medical Center, Amsterdam, Netherlands.
    Dorsman, Josephine
    VU Medical Center, Amsterdam, Netherlands.
    Smit, Egbert
    VU Medical Center, Amsterdam, Netherlands.
    Verheui, Henk
    VU Medical Center, Amsterdam, Netherlands.
    Reijneveld, Jaap
    VU Medical Center, Amsterdam, Netherlands.
    Tannous, Bakhos
    Massachusetts General Hospital, Boston, MA, USA.
    Wesseling, Pieter
    VU Medical Center, Amsterdam, Netherlands.
    Wurdinger, Thomas
    VU Medical Center, Amsterdam, Netherlands.
    Tumor-educated platelets allow for multiclass liquid biopsy-based diagnosis of cancer2015In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 75, no Suppl. 15, article id LB-124Article in journal (Other academic)
  • 99. Best, Myron
    et al.
    Sol, Nik
    Kooi, Irsan
    Nilsson, Jonas
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Westerman, Bart
    Ylstra, Bauke
    Dorsman, Josephine
    Smit, Egbert F
    Verheul, Henk M W
    Reijneveld, Jaap C
    Tannous, Bakhos A
    Wesseling, Pieter
    Wurdinger, Thomas
    Allowance of tumor-educated platelets for multiclass liquid biopsy-based diagnosis of cancer2015In: Journal of Clinical Oncology, ISSN 0732-183X, E-ISSN 1527-7755, Vol. 33, no 15, suppl., article id 11058Article in journal (Other academic)
  • 100. Bethke, Lara
    et al.
    Murray, Anne
    Webb, Emily
    Schoemaker, Minouk
    Muir, Kenneth
    McKinney, Patricia
    Hepworth, Sarah
    Dimitropoulou, Polyxeni
    Lophatananon, Artitaya
    Feychting, Maria
    Lönn, Stefan
    Ahlbom, Anders
    Malmer, Beatrice
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Henriksson, Roger
    Umeå University, Faculty of Medicine, Department of Radiation Sciences, Oncology.
    Auvinen, Anssi
    Kiuru, Anne
    Salminen, Tiina
    Johansen, Christoffer
    Collatz Christensen, Helle
    Kosteljanetz, Michael
    Swerdlow, Anthony
    Houlston, Richard
    Comprehensive analysis of DNA repair gene variants and risk of meningioma2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 4, p. 270-276Article in journal (Refereed)
    Abstract [en]

    Background: Meningiomas account for up to 37% of all primary brain tumors. Genetic susceptibility to meningioma is well established, with the risk among relatives of meningioma patients being approximately threefold higher than that in the general population. A relationship between risk of meningioma and exposure to ionizing radiation is also well known and led us to examine whether variants in DNA repair genes contribute to disease susceptibility.

    Methods: We analyzed 1127 tagging single-nucleotide polymorphisms (SNPs) that were selected to capture most of the common variation in 136 DNA repair genes in five case–control series (631 case patients and 637 control subjects) from four countries in Europe. We also analyzed 388 putative functional SNPs in these genes for their association with meningioma. All statistical tests were two-sided.

    Results: The SNP rs4968451, which maps to intron 4 of the gene that encodes breast cancer susceptibility gene 1–interacting protein 1, was consistently associated with an increased risk of developing meningioma. Across the five studies, the association was highly statistically significant (trend odds ratio = 1.57, 95% confidence interval = 1.28 to 1.93; Ptrend = 8.95 × 10−6; P = .009 after adjusting for multiple testing).

    Conclusions: We have identified a novel association between rs4968451 and meningioma risk. Because approximately 28% of the European population are carriers of at-risk genotypes for rs4968451, the variant is likely to make a substantial contribution to the development of meningioma.

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