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Title: Genome-wide Association Study Of Survival In Patients With Pancreatic Adenocarcinoma
Author: Wu, Chen
Kraft, Peter
Stolzenberg-Solomon, Rachael Z.
Steplowski, Emily
Brotzman, Michelle
Xu, Mousheng
Mudgal, Poorva
Amundadottir, Laufey
Arslan, Alan A.
Bueno de Mesquita, H. Bas
Gross, Myron
Helzlsouer, Kathy
Jacobs, Eric J.
Kooperberg, Charles
Petersen, Gloria M.
Zheng, Wei
Albanes, Demetrius
Boutron-Ruault, Marie-Christine
Buring, Julie E.
Canzian, Federico
Cao, Guangwen
Duell, Eric J.
Elena, Joanne L.
Gaziano, J. Michael
Giovannucci, Edward L.
Hallmans, Göran
Hutchinson, Amy
Hunter, David J.
Jenab, Mazda
Jiang, Guoliang
Khaw, Kay-Tee
LaCroix, Andrea
Li, Zhaoshen
Mendelsohn, Julie B.
Panico, Salvatore
Patel, Alpa V.
Qian, Zhirong
Sesso, Howard
Shen, Hongbing
Shu, Xiao-Ou
Tjønneland, Anne
Tobias, Geoffrey S.
Trichopoulos, Dimitrios
Virtamo, Jarmo
Visvanathan, Kala
Wactawski-Wende, Jean
Wang, Chengfeng
Yu, Kai
Zeleniuch-Jacquotte, Anne
Chanock, Stephen
Hoover, Robert
Hartge, Patricia
Fuchs, Charles S.
Lin, Dongxin
Wolpin, Brian M.
Keywords: Càncer de pàncrees
Polimorfisme genètic
Pancreas cancer
Genetic polymorphisms
Issue Date: 1-Jan-2014
Publisher: BMJ Publishing Group
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.
Note: Versió postprint del document publicat a:
It is part of: Gut, 2014, vol. 63, num. 1
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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