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. 2009 Sep;41(9):986-90.
doi: 10.1038/ng.429. Epub 2009 Aug 2.

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 Canzian, Françoise Clavel-Chapelon, Sandra Clipp, Michelle Cotterchio, Mariza de Andrade, Eric J Duell, John W Fox Jr, 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

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

Laufey Amundadottir et al. Nat Genet. 2009 Sep.

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.

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Figures

Figure 1
Figure 1. Manhattan plot of the P values in the pancreatic cancer GWAS
The association with pancreatic cancer is shown for the entire GWAS (12 cohort studies, and the Mayo case-control study, see Online Methods) (A), and the results of the GWAS including only the 12 cohorts studies (B). Association was assessed using unconditional logistic regression adjusted for study, arm, age, sex, ancestry and the top five principal components of the population stratification analysis. The x axis represents chromosomal locations and the y axis shows P values on a logarithmic scale.
Figure 2
Figure 2. Association and linkage disequilibrium plot of the 9q34 locus
Association results are shown for all GWAS studies (blue diamonds), GWAS cohorts (green diamonds), replication studies (red circles) and all studies combined (yellow circles). Overlaid on the association panel is a plot of estimated recombination rates (cM/Mb) across the region from HapMap Phase II. The LD plot shows a region of chromosome 9 marked by SNPs, rs505922 and rs630014 (r2=0.52 in HapMap CEU and 0.40 in PanScan European control individuals) and bounded by SNPs between chr9; 135,083,020-135,176,984 (NCBI Genome build 36). LD is depicted for SNPs with MAF > 5% within PanScan. Controls of European background (n=1,799 unrelated individuals). Note that rs505922 and rs630014 are located in the first intron of the ABO gene, shown above the LD plot. Only SNPs genotyped in both the GWAS and “Fast Track” replication are shown.
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