A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer
Julius Gudmundsson, Patrick Sulem, Daniel F Gudbjartsson, Gisli Masson, Bjarni A Agnarsson, Kristrun R Benediktsdottir, Asgeir Sigurdsson, Olafur Th Magnusson, Sigurjon A Gudjonsson, Droplaug N Magnusdottir, Hrefna Johannsdottir, Hafdis Th Helgadottir, Simon N Stacey, Adalbjorg Jonasdottir, Stefania B Olafsdottir, 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 Einarsson, Rosa B Barkardottir, Eirikur Jonsson, Dana Mates, David E Neal, Lambertus A Kiemeney, Unnur Thorsteinsdottir, Thorunn Rafnar, Kari Stefansson, Julius Gudmundsson, Patrick Sulem, Daniel F Gudbjartsson, Gisli Masson, Bjarni A Agnarsson, Kristrun R Benediktsdottir, Asgeir Sigurdsson, Olafur Th Magnusson, Sigurjon A Gudjonsson, Droplaug N Magnusdottir, Hrefna Johannsdottir, Hafdis Th Helgadottir, Simon N Stacey, Adalbjorg Jonasdottir, Stefania B Olafsdottir, 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 Einarsson, Rosa B Barkardottir, Eirikur Jonsson, Dana Mates, David E Neal, Lambertus A Kiemeney, Unnur Thorsteinsdottir, Thorunn Rafnar, Kari Stefansson
Abstract
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.
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Source: PubMed