Genome-wide association study of survival in patients with pancreatic adenocarcinoma
Year: 2012
Type: article
Study design: Observational Study
Abstract: BACKGROUND AND OBJECTIVE: Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genome-wide association study (GWAS) to identify germline variants associated with survival in patients with pancreatic adenocarcinoma. METHODS: We analysed overall survival in relation to single nucleotide polymorphisms (SNPs) among 1005 patients from two large GWAS datasets, PanScan I and ChinaPC. Cox proportional hazards regression was used in an additive genetic model with adjustment for age, sex, clinical stage and the top four principal components of population stratification. The first stage included 642 cases of European ancestry (PanScan), from which the top SNPs (p≤10(-5)) were advanced to a joint analysis with 363 additional patients from China (ChinaPC). RESULTS: In the first stage of cases of European descent, the top-ranked loci were at chromosomes 11p15.4, 18p11.21 and 1p36.13, tagged by rs12362504 (p=1.63×10(-7)), rs981621 (p=1.65×10(-7)) and rs16861827 (p=3.75×10(-7)), respectively. 131 SNPs with p≤10(-5) were advanced to a joint analysis with cases from the ChinaPC study. In the joint analysis, the top-ranked SNP was rs10500715 (minor allele frequency, 0.37; p=1.72×10(-7)) on chromosome 11p15.4, which is intronic to the SET binding factor 2 (SBF2) gene. The HR (95% CI) for death was 0.74 (0.66 to 0.84) in PanScan I, 0.79 (0.65 to 0.97) in ChinaPC and 0.76 (0.68 to 0.84) in the joint analysis. CONCLUSIONS: Germline genetic variation in the SBF2 locus was associated with overall survival in patients with pancreatic adenocarcinoma of European and Asian ancestry. This association should be investigated in additional large patient cohorts.
Source: Gut
Authors: Chen Wu, Peter Kraft, Rachael Stolzenberg-Solomon, Emily Steplowski, Michelle Brotzman, Mousheng Xu, Poorva Mudgal, Laufey Amundadottir, Alan A Arslan, H Bas Bueno-de-Mesquita, Myron Gross, Kathy Helzlsouer, Eric J Jacobs, Charles Kooperberg, Gloria M Petersen, Wei Zheng, Demetrius Albanes, Marie-Christine Boutron-Ruault, Julie E Buring, Federico Canzian, Guangwen Cao, Eric J Duell, Joanne W Elena, J Michael Gaziano, Edward L Giovannucci, Goran Hallmans, Amy Hutchinson, David J Hunter, Mazda Jenab, Guoliang Jiang, Kay-Tee Khaw, Andrea LaCroix, Zhaoshen Li, Julie B Mendelsohn, Salvatore Panico, Alpa V Patel, Zhi Rong Qian, Elio Riboli, Howard Sesso, Hongbing Shen, Xiao-Ou Shu, Anne Tjonneland, Geoffrey S Tobias, Dimitrios Trichopoulos, Jarmo Virtamo, Kala Visvanathan, Jean Wactawski-Wende, Chengfeng Wang, Kai Yu, Anne Zeleniuch-Jacquotte, Stephen Chanock, Robert Hoover, Patricia Hartge, Charles S Fuchs, Dongxin Lin, Brian M Wolpin
Institutions: Harvard University, Chinese Academy of Medical Sciences & Peking Union Medical College, State Key Laboratory of Molecular Oncology, National Institutes of Health, National Cancer Institute, Division of Cancer Epidemiology and Genetics, Information Management Services, Westat (United States), New York University, Utrecht University, University Medical Center Utrecht, National Institute for Public Health and the Environment, University of Minnesota, University of Minnesota System, Mercy Medical Center, Johns Hopkins University, American Cancer Society, Fred Hutch Cancer Center, Mayo Clinic, Vanderbilt University, Vanderbilt-Ingram Cancer Center, Inserm, Institut Gustave Roussy, Brigham and Women's Hospital, German Cancer Research Center, Second Military Medical University, Institut d'Investigació Biomédica de Bellvitge, Institut Català d'Oncologia, VA Boston Healthcare System, Umeå University, Science Applications International Corporation (United States), Centre international de recherche sur le cancer, Fudan University, Fudan University Shanghai Cancer Center, University of Cambridge, Addenbrooke's Hospital, Federico II University Hospital, University of Naples Federico II, Dana-Farber Cancer Institute, Imperial College London, Nanjing Medical University, Danish Cancer Society, Academy of Athens, Finnish Institute for Health and Welfare, Sidney Kimmel Comprehensive Cancer Center, University at Buffalo, State University of New York
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: G1011819373, G1060151506, Dana Farber/ Harvard Cancer Center SPORE in Gastrointestinal Cancer, G1168185457, G1294540475, G1327305488, G1423636853, G1553865127, G1638177084, DNA Repair, Skin Cancer and Overall Cancer Risk, G1734361364, Prospective Cohort Collaborative in Pancreatic Cancer Epidemiology & Pathogenesis, G1828895303, Cohort Study of Biochemical and Genetic Risk Factors for Pancreatic Cancer, G1963369394, G2099427675, G2145550945, G2176833112, G2788466971, G2802736426, FOLLOW-UP OF THE ALPHA-TOCOPHEROL, BETA-CAROTENE CANCER PREVENTION (ATBC) STUDY , Cancer Risk Reduction and Diet: A Cohort Study of Women, U S-FINLAND STUDIES OF NUTRITION AND CANCER, G386607036, Dietary and Hormonal Determinants of Cancer in Women, Vitamin D, Related Genes and Breast Cancer Risk, PREVENTIVE ONCOLOGY ACADEMIC AWARD, G4225032190, COORDINATING CENTER FOR WOMEN'S HEALTH INITIATIVE, G4522543292, G4582778782, G5108308032, G519175825, Physicians' Health Study II: Prevention Trial of Vitamins, G5684079324, G5884795238, G5888954722, G5897142711, G6124801312, G630576673, TRIAL OF ASPIRIN AND BETA-CAROTENE IN U S MD'S, G6766166885, Prospective Studies of Diet and Cancer in Men and Women, G7238814555, Women's Health Study: Continued Follow-up, G8554986239, G8749110163, G8844832511, G885693336, G9000072420, Mayo Clinic Comprehensive Cancer Center Support Grant, Cancer Center Support Grant
OpenAlex ID: W2118705337