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

34 Citations (Scopus)

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

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Genome-Wide Association Study
Adenocarcinoma
Single Nucleotide Polymorphism
Survival
Chromosomes, Human, Pair 7
Genetic Models
Gene Frequency
China
Chromosomes
Population
Genes

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Wu, C., Kraft, P., Stolzenberg-Solomon, R., Steplowski, E., Brotzman, M., Xu, M., ... 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

Genome-wide association study of survival in patients with pancreatic adenocarcinoma. / Wu, Chen; Kraft, Peter; Stolzenberg-Solomon, Rachael; 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 W.; Gaziano, J. Michael; Giovannucci, Edward L.; Hallmans, Goran; 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, Zhi Rong; Riboli, Elio; Sesso, Howard; Shen, Hongbing; Shu, Xiao Ou; Tjonneland, 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.

In: Gut, Vol. 63, No. 1, 01.2014, p. 152-160.

Research output: Contribution to journalArticle

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, S, Patel, AV, Qian, ZR, Riboli, E, Sesso, H, Shen, H, Shu, XO, Tjonneland, A, Tobias, GS, Trichopoulos, D, Virtamo, J, Visvanathan, K, Wactawski-Wende, J, Wang, C, Yu, K, Zeleniuch-Jacquotte, A, Chanock, S, Hoover, R, Hartge, P, Fuchs, CS, Lin, D & Wolpin, BM 2014, 'Genome-wide association study of survival in patients with pancreatic adenocarcinoma', Gut, vol. 63, no. 1, pp. 152-160. https://doi.org/10.1136/gutjnl-2012-303477
Wu C, Kraft P, Stolzenberg-Solomon R, Steplowski E, Brotzman M, Xu M et al. Genome-wide association study of survival in patients with pancreatic adenocarcinoma. Gut. 2014 Jan;63(1):152-160. https://doi.org/10.1136/gutjnl-2012-303477
Wu, Chen ; Kraft, Peter ; Stolzenberg-Solomon, Rachael ; 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 W. ; Gaziano, J. Michael ; Giovannucci, Edward L. ; Hallmans, Goran ; 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, Zhi Rong ; Riboli, Elio ; Sesso, Howard ; Shen, Hongbing ; Shu, Xiao Ou ; Tjonneland, 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. / Genome-wide association study of survival in patients with pancreatic adenocarcinoma. In: Gut. 2014 ; Vol. 63, No. 1. pp. 152-160.
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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.",
author = "Chen Wu and Peter Kraft and Rachael Stolzenberg-Solomon and Emily Steplowski and Michelle Brotzman and Mousheng Xu and Poorva Mudgal and Laufey Amundadottir and Arslan, {Alan A.} and Bueno-De-Mesquita, {H. Bas} and Myron Gross and Kathy Helzlsouer and Jacobs, {Eric J.} and Charles Kooperberg and Petersen, {Gloria M} and Wei Zheng and Demetrius Albanes and Boutron-Ruault, {Marie Christine} and Buring, {Julie E.} and Federico Canzian and Guangwen Cao and Duell, {Eric J.} and Elena, {Joanne W.} and Gaziano, {J. Michael} and Giovannucci, {Edward L.} and Goran Hallmans and Amy Hutchinson and Hunter, {David J.} and Mazda Jenab and Guoliang Jiang and Khaw, {Kay Tee} and Andrea LaCroix and Zhaoshen Li and Mendelsohn, {Julie B.} and Salvatore Panico and Patel, {Alpa V.} and Qian, {Zhi Rong} and Elio Riboli and Howard Sesso and Hongbing Shen and Shu, {Xiao Ou} and Anne Tjonneland and Tobias, {Geoffrey S.} and Dimitrios Trichopoulos and Jarmo Virtamo and Kala Visvanathan and Jean Wactawski-Wende and Chengfeng Wang and Kai Yu and Anne Zeleniuch-Jacquotte and Stephen Chanock and Robert Hoover and Patricia Hartge and Fuchs, {Charles S.} and Dongxin Lin and Wolpin, {Brian M.}",
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TY - JOUR

T1 - Genome-wide association study of survival in patients with pancreatic adenocarcinoma

AU - Wu, Chen

AU - Kraft, Peter

AU - Stolzenberg-Solomon, Rachael

AU - Steplowski, Emily

AU - Brotzman, Michelle

AU - Xu, Mousheng

AU - Mudgal, Poorva

AU - Amundadottir, Laufey

AU - Arslan, Alan A.

AU - Bueno-De-Mesquita, H. Bas

AU - Gross, Myron

AU - Helzlsouer, Kathy

AU - Jacobs, Eric J.

AU - Kooperberg, Charles

AU - Petersen, Gloria M

AU - Zheng, Wei

AU - Albanes, Demetrius

AU - Boutron-Ruault, Marie Christine

AU - Buring, Julie E.

AU - Canzian, Federico

AU - Cao, Guangwen

AU - Duell, Eric J.

AU - Elena, Joanne W.

AU - Gaziano, J. Michael

AU - Giovannucci, Edward L.

AU - Hallmans, Goran

AU - Hutchinson, Amy

AU - Hunter, David J.

AU - Jenab, Mazda

AU - Jiang, Guoliang

AU - Khaw, Kay Tee

AU - LaCroix, Andrea

AU - Li, Zhaoshen

AU - Mendelsohn, Julie B.

AU - Panico, Salvatore

AU - Patel, Alpa V.

AU - Qian, Zhi Rong

AU - Riboli, Elio

AU - Sesso, Howard

AU - Shen, Hongbing

AU - Shu, Xiao Ou

AU - Tjonneland, Anne

AU - Tobias, Geoffrey S.

AU - Trichopoulos, Dimitrios

AU - Virtamo, Jarmo

AU - Visvanathan, Kala

AU - Wactawski-Wende, Jean

AU - Wang, Chengfeng

AU - Yu, Kai

AU - Zeleniuch-Jacquotte, Anne

AU - Chanock, Stephen

AU - Hoover, Robert

AU - Hartge, Patricia

AU - Fuchs, Charles S.

AU - Lin, Dongxin

AU - Wolpin, Brian M.

PY - 2014/1

Y1 - 2014/1

N2 - 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.

AB - 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.

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