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dc.contributor.authorMatejcic, Marcoes_ES
dc.contributor.authorSaunders, Edward J.es_ES
dc.contributor.authorDadaev, Tokhires_ES
dc.contributor.authorBrook, Mark N.es_ES
dc.contributor.authorWang, Kanes_ES
dc.contributor.authorSheng, Xines_ES
dc.contributor.authorOlama, Ali Amin Ales_ES
dc.contributor.authorSchumacher, Fredrick R.es_ES
dc.contributor.authorIngles, Sue A.es_ES
dc.contributor.authorGovindasami, Koveelaes_ES
dc.contributor.authorBenlloch, Saraes_ES
dc.contributor.authorBerndt, Sonja I.es_ES
dc.contributor.authorAlbanes, Demetriuses_ES
dc.contributor.authorKoutros, Stellaes_ES
dc.contributor.authorMuir, Kennethes_ES
dc.contributor.authorStevens, Victoria L.es_ES
dc.contributor.authorGapstur, Susan M.es_ES
dc.contributor.authorLlorca Díaz, Francisco Javier es_ES
dc.contributor.authorDierssen Sotos, Trinidad es_ES
dc.contributor.authorGómez Acebo, Inés es_ES
dc.contributor.otherUniversidad de Cantabriaes_ES
dc.description.abstractChromosome 8q24 is a susceptibility locus for multiple cancers, including prostate cancer. Here we combine genetic data across the 8q24 susceptibility region from 71,535 prostate cancer cases and 52,935 controls of European ancestry to define the overall contribution of germline variation at 8q24 to prostate cancer risk. We identify 12 independent risk signals for prostate cancer (p?<?4.28?×?10-15), including three risk variants that have yet to be reported. From a polygenic risk score (PRS) model, derived to assess the cumulative effect of risk variants at 8q24, men in the top 1% of the PRS have a 4-fold (95%CI?=?3.62-4.40) greater risk compared to the population average. These 12 variants account for ~25% of what can be currently explained of the familial risk of prostate cancer by known genetic risk factors. These findings highlight the overwhelming contribution of germline variation at 8q24 on prostate cancer risk which has implications for population risk stratification.es_ES
dc.description.sponsorshipGenotyping of the OncoArray was funded by the US National Institutes of Health (NIH) [U19 CA 148537 for ELucidating Loci Involved in Prostate Cancer SuscEptibility (ELLIPSE) project and X01HG007492 to the Center for Inherited Disease Research (CIDR) under contract number HHSN268201200008I]. Additional analytic support was provided by NIH NCI U01 CA188392 (PI: Schumacher). The PRACTICAL consortium ( was supported by Cancer Research UK Grants C5047/A7357, C1287/A10118, C1287/A16563, C5047/A3354, C5047/A10692, C16913/A6135, European Commission's Seventh Framework Programme grant agreement n° 223175 (HEALTH-F2-2009-223175), and The National Institute of Health (NIH) Cancer Post-Cancer GWAS initiative grant: No. 1 U19 CA 148537-01 (the GAME-ON initiative). We wish to thank all GWAS study groups contributing to the data set from which this study was conducted: OncoArray; iCOGS; The PRACTICAL (Prostate Cancer Association Group to Investigate Cancer-Associated Alterations in the Genome) Consortium; and The GAME-ON/ELLIPSE Consortium. Detailed acknowledgements and funding information for all GWAS study groups and from all the individual studies involved in the PRACTICAL Consortium are included in Supplementary Note 1. We would also like to thank the following for funding support: The Institute of Cancer Research and The Everyman Campaign, The Prostate Cancer Research Foundation, Prostate Research Campaign UK (now Prostate Action), The Orchid Cancer Appeal, The National Cancer Research Network UK, The National Cancer Research Institute (NCRI) UK. We are grateful for support of NIHR funding to the NIHR Biomedical Research Centre at The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust.es_ES
dc.format.extent11 p.es_ES
dc.publisherNature Publishing Groupes_ES
dc.rightsAttribution 4.0 International*
dc.sourceNat Commun. 2018 Nov 5;9(1):4616es_ES
dc.titleGermline variation at 8q24 and prostate cancer risk in men of European ancestryes_ES

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Attribution 4.0 InternationalExcept where otherwise noted, this item's license is described as Attribution 4.0 International