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 × 10−11, per-allele odds ratio (OR) 1.26, 95% CI 1.18–1.35) and rs9564966 (P = 5.86 × 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 × 10−10, per-allele OR 0.77, 95% CI 0.71–0.84). A single SNP, rs401681 (P = 3.66 × 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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Acknowledgements
The authors gratefully acknowledge the energy and contribution of our late colleague Sheila Bingham. Additional acknowledgments are in the Supplementary Note.
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G.M.P., L.A., C.S.F., P.K., R.Z.S.-S., K.B.J., S.M.L., J.B.M., G.S.T., R.N.H., P.H. and S.J.C. 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., H.P., Z.W., K.Y., R.N.H., P.H. and S.J.C. contributed to the design and execution of statistical analysis. L.A., G.M.P., P.K., R.Z.S.-S., R.N.H., P.H. and S.J.C. wrote the first draft of the manuscript. G.M.P., C.S.F., R.Z.S.-S., A.A.A., H.B.B., S.G., M.G., K.H., E.A.H., E.J.J., A.P.K., A.L., D.L., M.T.M., S.H.O., H.A.R., W.Z., D.A., W.R.B., C.D.B., M.-C.B.-R., J.E.B., P.M.B., F.C., S.C., M.C., M.deA., E.J.D., J.M.G., E.L.G., M.G., G.H., S.E.H., M.H., B.H., D.J.H., M.J., R.K., V.K., R.C.K., R.R.M., D.S.M., A.V.P., P.H.M.P., A.R., E.R., L.R., X.-O.S., A.T., D.T., S.K.V.D.E., J.V., J.W.-W., B.M.W., H.Y., A.Z.-J. and J.F.F.Jr. conducted the epidemiologic studies and contributed samples to the PanScan GWAS and/or replication. All authors contributed to the writing of the manuscript.
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Petersen, G., Amundadottir, L., Fuchs, C. et al. A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Nat Genet 42, 224–228 (2010). https://doi.org/10.1038/ng.522
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DOI: https://doi.org/10.1038/ng.522
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