Scientists find HOXB13 mutation in 3.1% of men with early-onset, familial prostate cancer.

Investigators have identified a germline gene mutation that appears to markedly increase the risk of inherited prostate cancer. A team led by researchers at the Johns Hopkins University School of Medicine, and University of Michigan Health System, screened over 200 genes within 17q21–22, a region that has previously been implicated in prostate cancer.

Their results, reported in NEJM, highlighted a rare, recurrent mutation (G84E) in HOXB13, (rs138213197), in all 18 affected members of four prostate cancer families. HOXB13 is a homeobox transcription factor involved in prostate development. Analyses of additional cases and controls found that the G84E mutation was also carried by about 1.4% of unrelated prostate cancer patients of European descent, but by just 0.1% of control subjects. Further evaluation of prostate cancer cases indicated the mutation was also much more commonly found in men with early-onset, familial prostate cancer (3.1%) than in patients with late-onset, nonfamilial disease (0.6%).

Interestingly, two different mutations in the HOXB13 gene were found in families of African descent, but as only seven of the 94 families originally studied were of this ethnicity, additional work will be needed to verify its significance.

The researchers nevertheless point out that their identification of a single candidate gene involved in familial prostate cancer is the result of a 20-year hunt. “We had never seen anything like this before,” comments co-author Patrick Walsh, M.D., at Johns Hopkins. “It all came together to suggest that this single change may account for at least a portion of the hereditary form of this disease.”  

They team says the next step will be to develop a mouse model with the mutation and see whether it causes prostate cancer. Their published paper is titled “Germline Mutations in HOXB13 and Prostate-Cancer Risk.”

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