Abstract
We report a prostate cancer genome-wide association follow-on study. We discovered four variants associated with susceptibility to prostate cancer in several European populations: rs10934853[A] (OR = 1.12, P = 2.9 × 10−10) on 3q21.3; two moderately correlated (r2 = 0.07) variants, rs16902094[G] (OR = 1.21, P = 6.2 × 10−15) and rs445114[T] (OR = 1.14, P = 4.7 × 10−10), on 8q24.21; and rs8102476[C] (OR = 1.12, P = 1.6 × 10−11) on 19q13.2. We also refined a previous association signal on 11q13 with the SNP rs11228565[A] (OR = 1.23, P = 6.7 × 10−12). In a multivariate analysis using 22 prostate cancer risk variants typed in the Icelandic population, we estimated that carriers in the top 1.3% of the risk distribution are at a 2.5 times greater risk of developing the disease than members of the general population.
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Acknowledgements
We thank the individuals who participated in the study and whose contribution made this work possible. This project was funded in part by contract number 202059 (PROMARK) from the Seventh Framework Program of the European Union to deCODE Genetics (T.R. and L.A.K.), in part by FP7-MC-IAPP Grant agreement no. 218071 (CancerGene) to deCODE Genetics, in part by a V Foundation award and US Department of Veterans Affairs grants to J.R.S., and in part by Academy of Finland, Sigrid Juselius Foundation, Finnish Cancer Organisations and the Competitive Research Funding of the Pirkanmaa Hospital District, Tampere University Hospital, to J.S.
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The study was designed and results were interpreted by J. Gudmundsson, P.S., A.K., U.T., T.R. and K.S. Statistical analysis was carried out by P.S., D.F.G., J. Gudmundsson, M.L.F. and A.K. Subject recruitment, biological material collection and handling along with genotyping were supervised and carried out by J. Gudmundsson, B.A.A., K.R.B., T.B., A.G., D.N.M., G.O., M.J., S.N.S., A.S., T.W., T.T., J.P.B., K.M.M., K.M.B., B.S., J. Godino, S.N., F.F., L.M., E.P., K.K.A., I.M.v.O., B.K.S., B.T.H., D.K., C.Z., K.K., J.R.G., G.V.E., E.J., W.J.C., J.I.M., L.A.K., J.R.S., J.S., R.B.B., U.T. and T.R. Authors J. Gudmundsson, P.S., D.F.G., T.R. and K.S. drafted the manuscript. All authors contributed to the final version of the paper. Principal investigators and corresponding authors for the respective replication study populations are: The Netherlands, L.A.K.; Spain, J.I.M.; Chicago, W.J.C.; Nashville, Tenn., USA, J.R.S.; Finland, J.S.
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The authors from deCODE in Reykjavik, Iceland are shareholders in deCODE Genetics, Inc.
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Gudmundsson, J., Sulem, P., Gudbjartsson, D. et al. Genome-wide association and replication studies identify four variants associated with prostate cancer susceptibility. Nat Genet 41, 1122–1126 (2009). https://doi.org/10.1038/ng.448
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DOI: https://doi.org/10.1038/ng.448
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