J Gudmundsson, P Sulem, DF Gudbjartsson, G Masson, BA Agnarsson, KR Benediktsdottir, A Sigurdsson, OT Magnusson, SA Gudjonsson, DN Magnusdottir, H Johannsdottir, HT Helgadottir, SN Stacey, A Jonasdottir, SB Olafsdottir, G Thorleifsson, JG Jonasson, L Tryggvadottir, S Navarrete, F Fuertes, BT Helfand, Q Hu, IE Csiki, IN Mates, V Jinga, KKH Aben, IM van Oort, SH Vermeulen, JL Donovan, FC Hamdy, C-F Ng, PKF Chiu, K-M Lau, MCY Ng, JR Gulcher, A Kong, WJ Catalona, JI Mayordomo, GV Einarsson, RB Barkardottir, E Jonsson, D Mates, DE Neal, LA Kiemeney, U Thorsteinsdottir, T Rafnar, K Stefansson
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.