A study based on whole-genome sequencing yields a rare variant at 8q24 associated with prostate cancer.
Gudmundsson J., Sulem P., Gudbjartsson DF., Masson G., Agnarsson BA., Benediktsdottir KR., Sigurdsson A., Magnusson OT., Gudjonsson SA., Magnusdottir DN., Johannsdottir H., Helgadottir HT., Stacey SN., Jonasdottir A., Olafsdottir SB., Thorleifsson G., Jonasson JG., Tryggvadottir L., Navarrete S., Fuertes F., Helfand BT., Hu Q., Csiki IE., Mates IN., Jinga V., Aben KK., van Oort IM., Vermeulen SH., Donovan JL., Hamdy FC., Ng CF., Chiu PK., Lau KM., Ng MC., Gulcher JR., Kong A., Catalona WJ., Mayordomo JI., Einarsson GV., Barkardottir RB., Jonsson E., Mates D., Neal DE., Kiemeney LA., Thorsteinsdottir U., Rafnar T., Stefansson K.
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.