RT Journal Article
SR Electronic
T1 Genome-wide association study of survival in patients with pancreatic adenocarcinoma
JF Gut
JO Gut
FD BMJ Publishing Group Ltd and British Society of Gastroenterology
SP 152
OP 160
DO 10.1136/gutjnl-2012-303477
VO 63
IS 1
A1 Chen Wu
A1 Peter Kraft
A1 Rachael Stolzenberg-Solomon
A1 Emily Steplowski
A1 Michelle Brotzman
A1 Mousheng Xu
A1 Poorva Mudgal
A1 Laufey Amundadottir
A1 Alan A Arslan
A1 H Bas Bueno-de-Mesquita
A1 Myron Gross
A1 Kathy Helzlsouer
A1 Eric J Jacobs
A1 Charles Kooperberg
A1 Gloria M Petersen
A1 Wei Zheng
A1 Demetrius Albanes
A1 Marie-Christine Boutron-Ruault
A1 Julie E Buring
A1 Federico Canzian
A1 Guangwen Cao
A1 Eric J Duell
A1 Joanne W Elena
A1 J Michael Gaziano
A1 Edward L Giovannucci
A1 Goran Hallmans
A1 Amy Hutchinson
A1 David J Hunter
A1 Mazda Jenab
A1 Guoliang Jiang
A1 Kay-Tee Khaw
A1 Andrea LaCroix
A1 Zhaoshen Li
A1 Julie B Mendelsohn
A1 Salvatore Panico
A1 Alpa V Patel
A1 Zhi Rong Qian
A1 Elio Riboli
A1 Howard Sesso
A1 Hongbing Shen
A1 Xiao-Ou Shu
A1 Anne Tjonneland
A1 Geoffrey S Tobias
A1 Dimitrios Trichopoulos
A1 Jarmo Virtamo
A1 Kala Visvanathan
A1 Jean Wactawski-Wende
A1 Chengfeng Wang
A1 Kai Yu
A1 Anne Zeleniuch-Jacquotte
A1 Stephen Chanock
A1 Robert Hoover
A1 Patricia Hartge
A1 Charles S Fuchs
A1 Dongxin Lin
A1 Brian M Wolpin
YR 2014
UL http://gut.bmj.com/content/63/1/152.abstract
AB 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.