HOXB13 mutations in a population-based, case-control study of prostate cancer

Prostate. 2013 May;73(6):634-41. doi: 10.1002/pros.22604. Epub 2012 Nov 5.


Background: Prostate cancer (PC) is the most frequently diagnosed non-skin malignancy in men in the Western world, yet few disease-associated mutations have been found. Recently, a low frequency recurring mutation in the HOXB13 gene was reported among both hereditary PC families and men from the general population.

Materials and methods: We determined the distribution and frequency of the G84E HOXB13 variant in 1,310 incipient PC cases and 1,259 age-mated controls from a population-based, case-control study of PC.

Results: The G84E mutation was more frequent in cases than controls (1.3% vs. 0.4%, respectively), and men with the HOXB13 G84E variant had a 3.3-fold higher relative risk of PC compared with noncarriers (95% CI, 1.21-8.96). There was a stronger association between the G84E variant and PC among men with no first-degree relative with PC (OR, 4.04; 95% CI, 1.12-14.51) compared to men with a family history of PC (OR, 1.49; 95% CI, 0.30-7.50; P = 0.36 for interaction). We observed some evidence of higher risk estimates associated with the variant for men with higher versus lower Gleason score (OR, 4.13; 95% CI, 1.38-12.38 vs. OR, 2.71; 95% CI, 0.88-8.30), and advanced versus local stage (OR, 4.47; 95% CI, 1.28-15.57 vs. OR, 2.98; 95% CI, 1.04-8.49), however these differences were not statistically different.

Conclusions: These results confirm the association of a rare HOXB13 mutation with PC in the general population and suggest that this variant may be associated with features of more aggressive disease.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Case-Control Studies
  • European Continental Ancestry Group / genetics
  • Genetic Predisposition to Disease / epidemiology
  • Genetic Predisposition to Disease / genetics
  • Genetics, Population
  • Genotype
  • History, 16th Century
  • Homeodomain Proteins / genetics*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Point Mutation / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Prostatic Neoplasms / epidemiology*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Risk Factors
  • Washington / epidemiology


  • HOXB13 protein, human
  • Homeodomain Proteins

Supplementary concepts

  • Prostate cancer, familial