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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 × 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.

Original publication

DOI

10.1038/ng.2437

Type

Journal article

Journal

Nat genet

Publication Date

12/2012

Volume

44

Pages

1326 - 1329

Keywords

Adenocarcinoma, Aged, Aged, 80 and over, Base Sequence, Cell Line, Chromosomes, Human, Pair 8, European Continental Ancestry Group, Gene Frequency, Genetic Predisposition to Disease, Genome, Human, Genome-Wide Association Study, Homeodomain Proteins, Humans, Iceland, Male, Middle Aged, Molecular Sequence Data, Mutation, Polymorphism, Single Nucleotide, Prostatic Neoplasms, Risk, Sequence Analysis, DNA