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PMID: 20101243 Published · ppublish English Journal Article

A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.

Nature genetics ·Vol. 42 ·No. 3 ·2010-03-00 ·Pages 224-8

Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg-Solomon RZ, Jacobs KB, Arslan AA, Bueno-de-Mesquita HB, Gallinger S, Gross M, Helzlsouer K, Holly EA, Jacobs EJ, Klein AP, LaCroix A, Li D, Mandelson MT, Olson SH, Risch HA, Zheng W, Albanes D, Bamlet WR, Berg CD, Boutron-Ruault MC, Buring JE, Bracci PM, Canzian F, Clipp S, Cotterchio M, de Andrade M, Duell EJ, Gaziano JM, Giovannucci EL, Goggins M, Hallmans G, Hankinson SE, Hassan M, Howard B, Hunter DJ, Hutchinson A, Jenab M, Kaaks R, Kooperberg C, Krogh V, Kurtz RC, Lynch SM, McWilliams RR, Mendelsohn JB, Michaud DS, Parikh H, Patel AV, Peeters PH, Rajkovic A, Riboli E, Rodriguez L, Seminara D, Shu XO, Thomas G, Tjønneland A, Tobias GS, Trichopoulos D, Van Den Eeden SK, Virtamo J, Wactawski-Wende J, Wang Z, Wolpin BM, Yu H, Yu K, Zeleniuch-Jacquotte A, Fraumeni JF, Hoover RN, Hartge P, Chanock SJ

Abstract

We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 x 10(-11), per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 x 10(-8), per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 x 10(-10), per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 x 10(-7), per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.

MeSH Terms
Carcinoma/genetics Case-Control Studies Chromosomes, Human, Pair 1 Chromosomes, Human, Pair 13 Chromosomes, Human, Pair 5 Cohort Studies Genetic Loci Genetic Predisposition to Disease/genetics Genome-Wide Association Study Humans Linkage Disequilibrium Pancreatic Neoplasms/genetics Polymorphism, Single Nucleotide
Authors & Affiliations
73 authors, click to expand affiliations / ORCID
Petersen Gloria M
Department of Health Sciences Research, College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.
Amundadottir Laufey
Fuchs Charles S
Kraft Peter
Stolzenberg-Solomon Rachael Z
Jacobs Kevin B
Arslan Alan A
Bueno-de-Mesquita H Bas
Gallinger Steven
Gross Myron
Helzlsouer Kathy
Holly Elizabeth A
Jacobs Eric J
Klein Alison P
LaCroix Andrea
Li Donghui
Mandelson Margaret T
Olson Sara H
Risch Harvey A
Zheng Wei
Albanes Demetrius
Bamlet William R
Berg Christine D
Boutron-Ruault Marie-Christine
Buring Julie E
Bracci Paige M
Canzian Federico
Clipp Sandra
Cotterchio Michelle
de Andrade Mariza
Duell Eric J
Gaziano J Michael
Giovannucci Edward L
Goggins Michael
Hallmans Göran
Hankinson Susan E
Hassan Manal
Howard Barbara
Hunter David J
Hutchinson Amy
Jenab Mazda
Kaaks Rudolf
Kooperberg Charles
Krogh Vittorio
Kurtz Robert C
Lynch Shannon M
McWilliams Robert R
Mendelsohn Julie B
Michaud Dominique S
Parikh Hemang
Patel Alpa V
Peeters Petra H M
Rajkovic Aleksandar
Riboli Elio
Rodriguez Laudina
Seminara Daniela
Shu Xiao-Ou
Thomas Gilles
Tjønneland Anne
Tobias Geoffrey S
Trichopoulos Dimitrios
Van Den Eeden Stephen K
Virtamo Jarmo
Wactawski-Wende Jean
Wang Zhaoming
Wolpin Brian M
Yu Herbert
Yu Kai
Zeleniuch-Jacquotte Anne
Fraumeni Joseph F
Hoover Robert N
Hartge Patricia
Chanock Stephen J
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Article Info
Journal
Nature genetics
Abbr.
Nat Genet
ISSN
1546-1718
DOI
10.1038/ng.522
Published
2010-03-00
Epub
2010-00-24
Pages
224-8
Language
English
Region
United States
NLM ID
9216904
PMCID
PMC2853179
Subset
IM
Grants
NCI NIH HHS · P50 CA062924-130011 · United States
NCI NIH HHS · R01 CA082729 · United States
NCI NIH HHS · P50 CA062924 · United States
NCI NIH HHS · P50 CA062924-140011 · United States
NCI NIH HHS · R37 CA070867 · United States
Intramural NIH HHS · ZIA CP010193-03 · United States
NCI NIH HHS · R01 CA124908 · United States
NCI NIH HHS · P50 CA102701 · United States
NCI NIH HHS · K07 CA140790 · United States
NCI NIH HHS · R01 CA097193 · United States
NCI NIH HHS · P50 CA062924-150011 · United States
NCI NIH HHS · P50 CA062924-160011 · United States
External Links
PubMed source DOI: 10.1038/ng.522 PMC Full Text View journal details
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