Journal
NATURE GENETICS
Volume 44, Issue 12, Pages 1326-1329Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2437
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Funding
- European Union [202059]
- Urological Research Foundation [U01 CA089600, P50 CA90386, P30 CA60553]
- Health Technology Assessment Programme [96/20/06, 96/20/99]
- Department of Health, England
- Cancer Research UK [C522/A8649]
- Medical Research Council of England [G0500966_ID-75466]
- National Cancer Research Institute (NCRI), UK
- Southwest National Health Service Research and Development
- NCRI (ProMPT) study
- Cambridge and Oxford British Medical Research Council grants from the National Institute for Health Research
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In Western countries, prostate cancer is the most prevalent cancer of men and one of the leading causes of cancer-related death in men. Several genome-wide association studies have yielded numerous common variants conferring risk of prostate cancer. Here, we analyzed 32.5 million variants discovered by whole-genome sequencing 1,795 Icelanders. We identified a new low-frequency variant at 8q24 associated with prostate cancer in European populations, rs188140481[A] (odds ratio (OR) 2.90; P-combined = 6.2 x 10(-34)), with an average risk allele frequency in controls of 0.54%. This variant is only very weakly correlated (r(2) <= 0.06) with previously reported risk variants at 8q24, and its association remains significant after adjustment for all known risk-associated variants. Carriers of rs188140481[A] were diagnosed with prostate cancer 1.26 years younger than non-carriers (P = 0.0059). We also report results for a previously described HOXB13 variant (rs138213197[T]), confirming it as a prostate cancer risk variant in populations from across Europe.
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