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

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

Research output: Contribution to journalArticlepeer-review

553 Scopus citations

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 × 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.

Original languageEnglish
Pages (from-to)986-990
Number of pages5
JournalNature Genetics
Volume41
Issue number9
DOIs
StatePublished - Aug 2009

Keywords

  • ABO Blood-Group System/genetics
  • Alleles
  • Case-Control Studies
  • Chromosomes, Human, Pair 9
  • Cohort Studies
  • 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/genetics
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Risk Factors
  • United States

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