A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer

• DOI: 10.1038/ng.2437
• Publication Date: 2012-10-29T14:48:44Z
• Authors: Julius Gudmundsson; Patrick Sulem; Daniel F Gudbjart...; Gisli Masson; Bjarni A Agnarsson; Kristrun R Benedi...; Asgeir Sigurdsson; Olafur Th Magnusson; Sigurjon A Gudjon...; Droplaug N Magnus...; Hrefna Johannsdottir; Hafdis Th Helgado...; Simon N Stacey; Adalbjorg Jonasdo...; Stefania B Olafsd...; Gudmar Thorleifsson; Jon G Jonasson; Laufey Tryggvadottir; Sebastian Navarrete; Fernando Fuertes; Brian T Helfand; Qiaoyan Hu; Irma E Csiki; Ioan N Mates; Viorel Jinga; Katja K H Aben; Inge M van Oort; Sita H Vermeulen; Jenny L Donovan; Freddy C Hamdy; Chi-Fai Ng; Peter K F Chiu; Kin-Mang Lau; Maggie C Y Ng; Jeffrey R Gulcher; Augustine Kong; William J Catalona; Jose I Mayordomo; Gudmundur V Einar...; Rosa B Barkardottir; Eirikur Jonsson; Dana Mates; David E Neal; Lambertus A Kiemeney; Unnur Thorsteinsd...; Thorunn Rafnar; Kari Stefansson
• Keywords: Genome-wide Association Study

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 × 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.