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

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.

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Figure 1: Manhattan plot of the P values in the pancreatic cancer GWAS.
Figure 2: Association and linkage disequilibrium plot of the 9q34 locus.

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Acknowledgements

The authors gratefully acknowledge the energy and contribution of our late colleague, Robert Welch. Additional acknowledgments are found in the Supplementary Note.

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Contributions

L.A., P.K., R.Z.S.-S., C.S.F., G.M.P., K.B.J., S.M.L., J.B.M., G.S.T., S.J.C., P.H. and R.N.H. organized and designed the study. L.A., A.H., K.B.J., G.T. and S.J.C. supervised genotyping of samples. L.A., P.K., R.Z.S.-S., C.S.F., K.B.J., C.K., K.Y., S.J.C., P.H. and R.N.H. contributed to the design and execution of statistical analysis. LA., S.J.C., P.H. and R.N.H. wrote the first draft of the manuscript. R.Z.S.-S., C.S.F., G.M.P., A.A.A., H.B.B.-d.-M., M.G., K.H., E.J.J., A.L., W.Z., D.A., W.B., C.D.B., F.B., S.B., J.E.B., P.M.B., F.C., F.C.-C., S.C., M.C., M.d.A., E.J.D., J.W.F., S.G., J.M.G., E.L.G., M.G., C.A.G., G.H., S.E.H., M.H., E.A.H., D.J.H., R.J., M.J., R.K., A.P.K., C.K., R.C.K., D.L., M.M., R.R.M., D.S.M., S.H.O., K.O., A.V.P., P.H.M.P., A.R., E.R., H.A.R., X.-O.S., D.T., S.K.V.D.E., J.V., J.W.-W., B.M.W., H.Y. and A.Z.-J. conducted the epidemiologic studies and contributed samples to the PanScan GWAS and/or replication. All authors contributed to the writing of the manuscript.

Corresponding author

Correspondence to Stephen J Chanock.

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Supplementary Figures 1–4, Supplementary Tables 1–5 and Supplementary Note (PDF 401 kb)

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Amundadottir, L., Kraft, P., Stolzenberg-Solomon, R. et al. Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 41, 986–990 (2009). https://doi.org/10.1038/ng.429

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