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


  • The authors have no conflict of interest to disclose.

  • Marni Stott-Miller and Danielle M. Karyadi contributed equally to this work.



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.


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.


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.


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. Prostate 73: 634–641, 2013. © 2012 Wiley Periodicals, Inc.