Germline variation at 8q24 and prostate cancer risk in men of European ancestry
Marco Matejcic, Edward J Saunders, Tokhir Dadaev, Mark N Brook, Kan Wang, Xin Sheng, Ali Amin Al Olama, Fredrick R Schumacher, Sue A Ingles, Koveela Govindasami, Sara Benlloch, Sonja Berndt, Demetrius Albanes, Stella Koutros, Kenneth Muir, Victoria L Stevens, Susan M Gapstur, Catherine M Tangen, Jyotsna Batra, Judith Clements Show all
NATURE COMMUNICATIONS | NATURE PUBLISHING GROUP | Published : 2018
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 ..View full abstract
Related Projects (1)
PRECISION PUBLIC HEALTH FOR MAJOR CANCERS - NOVEL APPROACHES TO BUILDING THE GENETIC, EPIGENETIC AND LIFESTYLE KNOWLEDGE BASE FOR ASSESSING RISK AND PROGNOSIS
The Program of research seeks to increase our understanding of cancer risk. We will use our large collections of population and family-based..
Awarded by US National Institutes of Health (NIH)
Awarded by NIH NCI
Awarded by Cancer Research UK Grants
Awarded by European Commission's Seventh Framework Programme
Awarded by National Institute of Health (NIH) Cancer PostCancer GWAS
Awarded by NATIONAL CANCER INSTITUTE
Awarded by NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
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 no 223175 (HEALTH-F2-2009-223175), and The National Institute of Health (NIH) Cancer PostCancer 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.