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

2010; Nature Portfolio; Volume: 42; Issue: 3 Linguagem: Inglês

10.1038/ng.522

1546-1718

Gloria M. Petersen, Laufey T. Ámundadóttir, Charles S. Fuchs, Peter Kraft, Rachael Z. Stolzenberg‐Solomon, Kevin B. Jacobs, Alan A. Arslan, H. Bas Bueno‐de‐Mesquita, Steven Gallinger, Myron D. Gross, Kathy J. Helzlsouer, Elizabeth A. Holly, Eric J. Jacobs, Alison P. Klein, Andrea Z. LaCroix, Donghui Li, Margaret T. Mandelson, Sara H. Olson, Harvey A. Risch, Wei Zheng, Demetrius Albanes, William R. Bamlet, Christine D. Berg, Marie‐Christine Boutron‐Ruault, Julie E. Buring, Paige M. Bracci, Federico Canzian, Sandra Clipp, Michelle Cotterchio, Mariza de Andrade, Eric J. Duell, J. Michael Gaziano, Edward L. Giovannucci, Michael Goggins, Göran Hallmans, Susan E. Hankinson, Manal M. Hassan, Barbara V. Howard, David J. Hunter, Amy Hutchinson, Mazda Jenab, Rudolf Kaaks, Charles Kooperberg, Vittorio Krogh, Robert C. Kurtz, Shannon M. Lynch, Robert R. McWilliams, Julie B. Mendelsohn, Dominique S. Michaud, Hemang Parikh, Alpa V. Patel, Petra H. Peeters, Aleksandar Rajkovic, Elio Ríboli, Laudina Rodríguez, Daniela Seminara, Xiao‐Ou Shu, Gilles Thomas, Anne Tjønneland, Geoffrey S. Tobias, Dimitrios Trichopoulos, Stephen K. Van Den Eeden, Jarmo Virtamo, Jean Wactawski‐Wende, Zhaoming Wang, Brian M. Wolpin, Herbert Yu, Kai Yu, Anne Zeleniuch‐Jacquotte, Joseph F. Fraumeni, Robert N. Hoover, Patricia Hartge, Stephen J. Chanock,

MicroRNA in disease regulation

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.