Testing for the recurrent HOXB13 G84E germline mutation in men with clinical indications for prostate biopsy

The G84E variant of HOXB13 was recently found to be associated with a significantly increased risk of prostate cancer in a case control study. We estimated the prevalence of this mutation in a clinical population of men at risk for prostate cancer who were scheduled to undergo prostate biopsy.

We prospectively collected clinical information and DNA samples from men who underwent diagnostic prostate biopsy between June 2005 and October 2011. We genotyped samples for HOXB13 G84E using the MassARRAY® system. We determined the prevalence of the G84E variant in the overall cohort, among patients with a positive family history and among men age 55 years or younger.

A total of 1,175 subjects underwent biopsy, of whom 948 had a DNA sample for analysis. The G84E variant was detected in 4 patients (prevalence 0.42%, 95% CI 0.12-1.08), of whom 3 had prostate cancer on biopsy. None of 301 patients with a positive family history (prevalence 0.00%, 95% CI 0.00-1.22) and 1 of 226 patients age 55 years or younger tested positive (prevalence 0.44%, 95% CI 0.01-2.44).

The HOXB13 G84E variant is rare in this cohort, even among those with a positive family history. Our findings question the utility of testing for this variant among unselected men presenting for a diagnostic prostate biopsy.