Genome-wide association study of survival in patients with pancreatic adenocarcinoma

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 CanzianGuangwen 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

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Background and objective Survival of patients with pancreatic adenocarcinoma is limited and few prognostic factors are known. We conducted a two-stage genomewide 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=1.63times;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.

Original languageEnglish (US)
Pages (from-to)152-160
Number of pages9
JournalGut
Volume63
Issue number1
DOIs
StatePublished - Jan 2014

ASJC Scopus subject areas

  • Gastroenterology

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    Wu, C., Kraft, P., Stolzenberg-Solomon, R., Steplowski, E., Brotzman, M., Xu, M., Mudgal, P., Amundadottir, L., Arslan, A. A., Bueno-De-Mesquita, H. B., Gross, M., Helzlsouer, K., Jacobs, E. J., Kooperberg, C., Petersen, G. M., Zheng, W., Albanes, D., Boutron-Ruault, M. C., Buring, J. E., ... Wolpin, B. M. (2014). Genome-wide association study of survival in patients with pancreatic adenocarcinoma. Gut, 63(1), 152-160. https://doi.org/10.1136/gutjnl-2012-303477