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

Nat Genet. 2012 Dec;44(12):1326-9. doi: 10.1038/ng.2437. Epub 2012 Oct 28.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • HOXB13 protein, human
  • Homeodomain Proteins