1. Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma
- Author
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Kala Visvanathan, Jean Wactawski-Wende, Salvatore Panico, Andrea Z. LaCroix, Patricia Hartge, Charles S. Fuchs, Chen Wu, Mazda Jenab, Chengfeng Wang, Brian M. Wolpin, Poorva Mudgal, Anne Zeleniuch-Jacquotte, Kay-Tee Khaw, Laufey T. Amundadottir, Elio Riboli, Marie-Christine Boutron-Ruault, Edward Giovannucci, Wei Zheng, Federico Canzian, Guoliang Jiang, Emily Steplowski, Julie E. Buring, H. Bas Bueno-de-Mesquita, Myron D. Gross, Michelle Brotzman, Eric J. Jacobs, Joanne W. Elena, Demetrius Albanes, Eric J. Duell, Stephen J. Chanock, Dongxin Lin, Göran Hallmans, David J. Hunter, Charles Kooperberg, Geoffrey S. Tobias, Alan A. Arslan, Zhi Rong Qian, Guangwen Cao, Anne Tjønneland, Kathy J. Helzlsouer, Alpa V. Patel, Howard D. Sesso, Jarmo Virtamo, Rachael Z. Stolzenberg-Solomon, Robert N. Hoover, J. Michael Gaziano, Mousheng Xu, Hongbing Shen, Gloria M. Petersen, Kai Yu, Peter Kraft, Xiao-Ou Shu, Dimitrios Trichopoulos, Zhao-Shen Li, Julie B. Mendelsohn, Amy Hutchinson, Wu, C, Kraft, P, Stolzenberg Solomon, R, Steplowski, E, Brotzman, M, Xu, M, Mudgal, P, Amundadottir, L, Arslan, Aa, Bueno de Mesquita, Hb, Gross, M, Helzlsouer, K, Jacobs, Ej, Kooperberg, C, Petersen, Gm, Zheng, W, Albanes, D, Boutron Ruault, Mc, Buring, Je, Canzian, F, Cao, G, Duell, Ej, Elena, Jw, Gaziano, Jm, Giovannucci, El, Hallmans, G, Hutchinson, A, Hunter, Dj, Jenab, M, Jiang, G, Khaw, Kt, Lacroix, A, Li, Z, Mendelsohn, Jb, Panico, Salvatore, Patel, Av, Qian, Zr, Riboli, E, Sesso, H, Shen, H, Shu, Xo, Tjonneland, A, Tobias, G, Trichopoulos, D, Virtamo, J, Visvanathan, K, Wactawski Wende, J, Wang, C, Yu, K, Zeleniuch Jacquotte, A, Chanock, S, Hoover, R, Hartge, P, Fuchs, C, Lin, D, and Wolpin, Bm
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Oncology ,Male ,Genome-wide association study ,Kaplan-Meier Estimate ,Gastroenterology ,0302 clinical medicine ,Models ,80 and over ,2.1 Biological and endogenous factors ,Non-Receptor ,Pancreas cancer ,Cancer ,Aged, 80 and over ,0303 health sciences ,Principal Component Analysis ,Molecular Epidemiology ,Tumor ,Single Nucleotide ,Middle Aged ,Protein Tyrosine Phosphatases, Non-Receptor ,3. Good health ,Survival Rate ,Europe ,030220 oncology & carcinogenesis ,Adenocarcinoma ,Female ,Adult ,Asian Continental Ancestry Group ,medicine.medical_specialty ,China ,European Continental Ancestry Group ,Clinical Sciences ,and over ,Biology ,Genetic polymorphisms ,Polymorphism, Single Nucleotide ,White People ,Article ,Paediatrics and Reproductive Medicine ,03 medical and health sciences ,Pancreatic Cancer ,Rare Diseases ,Asian People ,Genetic ,Internal medicine ,Pancreatic cancer ,Biomarkers, Tumor ,medicine ,Cancer Genetics ,Genetics ,Humans ,In patient ,Polymorphism ,Càncer de pàncrees ,030304 developmental biology ,Proportional Hazards Models ,Aged ,Models, Genetic ,Molecular epidemiology ,Gastroenterology & Hepatology ,Prevention ,Polimorfisme genètic ,Human Genome ,medicine.disease ,Pancreatic Neoplasms ,Cancer genetics ,Protein Tyrosine Phosphatases ,Digestive Diseases ,Biomarkers ,Follow-Up Studies ,Genome-Wide Association 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 (p10(-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=1.63x10(-7)), rs981621 (p=1.65x10(-7)) and rs16861827 (p=3.75x10(-7)), respectively. 131 SNPs with p10(-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=1.72x10(-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.