A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33.
- Petersen, Gloria M;
- 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 HM;
- 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
- et al.
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.
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