TY - JOUR T1 - Genome-wide association study of survival in patients with pancreatic adenocarcinoma JF - Gut JO - Gut SP - 152 LP - 160 DO - 10.1136/gutjnl-2012-303477 VL - 63 IS - 1 AU - Chen Wu AU - Peter Kraft AU - Rachael Stolzenberg-Solomon AU - Emily Steplowski AU - Michelle Brotzman AU - Mousheng Xu AU - Poorva Mudgal AU - Laufey Amundadottir AU - Alan A Arslan AU - H Bas Bueno-de-Mesquita AU - Myron Gross AU - Kathy Helzlsouer AU - Eric J Jacobs AU - Charles Kooperberg AU - Gloria M Petersen AU - Wei Zheng AU - Demetrius Albanes AU - Marie-Christine Boutron-Ruault AU - Julie E Buring AU - Federico Canzian AU - Guangwen Cao AU - Eric J Duell AU - Joanne W Elena AU - J Michael Gaziano AU - Edward L Giovannucci AU - Goran Hallmans AU - Amy Hutchinson AU - David J Hunter AU - Mazda Jenab AU - Guoliang Jiang AU - Kay-Tee Khaw AU - Andrea LaCroix AU - Zhaoshen Li AU - Julie B Mendelsohn AU - Salvatore Panico AU - Alpa V Patel AU - Zhi Rong Qian AU - Elio Riboli AU - Howard Sesso AU - Hongbing Shen AU - Xiao-Ou Shu AU - Anne Tjonneland AU - Geoffrey S Tobias AU - Dimitrios Trichopoulos AU - Jarmo Virtamo AU - Kala Visvanathan AU - Jean Wactawski-Wende AU - Chengfeng Wang AU - Kai Yu AU - Anne Zeleniuch-Jacquotte AU - Stephen Chanock AU - Robert Hoover AU - Patricia Hartge AU - Charles S Fuchs AU - Dongxin Lin AU - Brian M Wolpin Y1 - 2014/01/01 UR - http://gut.bmj.com/content/63/1/152.abstract N2 - 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. ER -