Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.

Publication Type:

Journal Article

Authors:

Amundadottir, Laufey; Kraft, Peter; Stolzenberg-Solomon, Rachael Z; Fuchs, Charles S; Petersen, Gloria M; Arslan, Alan A; Bueno-de-Mesquita, H Bas; Gross, Myron; Helzlsouer, Kathy; Jacobs, Eric J; LaCroix, Andrea Z; Zheng, Wei; Albanes, Demetrius; Bamlet, William; Berg, Christine D; Berrino, Franco; Bingham, Sheila; Buring, Julie E; Bracci, Paige M; Canzian, Federico; Clavel-Chapelon, Françoise; Clipp, Sandra; Cotterchio, Michelle; de Andrade, Mariza; Duell, Eric J; Fox, John W; Gallinger, Steven; Gaziano, J Michael; Giovannucci, Edward L; Goggins, Michael; González, Carlos A; Hallmans, Göran; Hankinson, Susan E; Hassan, Manal; Holly, Elizabeth A; Hunter, David J; Hutchinson, Amy; Jackson, Rebecca; Jacobs, Kevin B; Jenab, Mazda; Kaaks, Rudolf; Klein, Alison P; Kooperberg, Charles; Kurtz, Robert C; Li, Donghui; Lynch, Shannon M; Mandelson, Margaret; McWilliams, Robert R; Mendelsohn, Julie B; Michaud, Dominique S; Olson, Sara H; Overvad, Kim; Patel, Alpa V; Peeters, Petra H M; Rajkovic, Aleksandar; Riboli, Elio; Risch, Harvey A; Shu, Xiao-Ou; Thomas, Gilles; Tobias, Geoffrey S; Trichopoulos, Dimitrios; Van Den Eeden, Stephen K; Virtamo, Jarmo; Wactawski-Wende, Jean; Wolpin, Brian M; Yu, Herbert; Yu, Kai; Zeleniuch-Jacquotte, Anne; Chanock, Stephen J; Hartge, Patricia; Hoover, Robert N

Source:

Nature genetics, Volume 41, Issue 9, p.986-90 (2009)

Keywords:

2009, ABO Blood-Group System, Alleles, Case-Control Studies, Center-Authored Paper, Chromosomes, Human, Pair 9, Cohort Studies, Collaborative Data Services Core Facility, Female, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Genotype, Haplotypes, Humans, Introns, LINKAGE DISEQUILIBRIUM, Logistic Models, Male, Odds Ratio, Pancreatic Neoplasms, Polymorphism, Single Nucleotide, Prospective Studies, Public Health Sciences Division, Risk Factors, Shared Resources, Specimen Processing Core Facility, United States

Abstract:

We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.