Germline variation at 8q24 and prostate cancer risk in men of European ancestry

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• dc.contributor.author Matejcic, Marco
• dc.contributor.author Kogevinas, Manolis
• dc.contributor.author Haiman, Christopher A.
• dc.date.accessioned 2019-06-14T07:39:36Z
• dc.date.available 2019-06-14T07:39:36Z
• dc.date.issued 2018
• dc.description.abstract Chromosome 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.
• dc.description.sponsorship Genotyping 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 (http://practical.icr.ac.uk/) 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.
• dc.format.mimetype application/pdf
• dc.identifier.citation Matejcic M, Saunders EJ, Dadaev T, Brook MN, Wang K, Sheng X. et al. Germline variation at 8q24 and prostate cancer risk in men of European ancestry. Nat Commun. 2018 Nov 5;9(1):4616. DOI: 10.1038/s41467-018-06863-1
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-018-06863-1
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/41755
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nature Communications . 2018 Nov 5;9(1):4616
• dc.relation.ispartof Nature Communications. 2018 Nov 5;9(1):4616
• dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/223175
• dc.rights Copyright © The Author(s) 2018. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.other Pròstata -- Càncer
• dc.title Germline variation at 8q24 and prostate cancer risk in men of European ancestry
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion