Researchers have discovered a rare but recurrent mutation that increases the risk of hereditary prostate cancer by up to 20 times.

Although the novel HOXB13 G84E variant accounts for only a small fraction of all prostate cancers, the mutation was found to be significantly more common in men with early-onset, familial prostate cancer than in those with late-onset, nonfamilial disease.

The HOXB13 gene plays an important role in prostate development in male fetuses and in the function of this gland later in life. Four different families with multiple cases of prostate cancer among first-degree relatives were found to have the G84E mutation in this gene, and all 18 family members with prostate cancer and available DNA were identified as carriers of the mutation.

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The carrier rate of the mutation was increased by a factor of approximately 20 in 5,083 unrelated subjects of European descent who had prostate cancer.    

G84E represents the first major genetic variant associated with inherited prostate cancer, according to Kathleen A. Cooney, MD, professor of internal medicine and urology at University of Michigan Medical School in Ann Arbor and one of the two senior authors of the study, which was published in The New England Journal of Medicine (2012;366[2]:141-149).

“[The mutation is] what we’ve been looking for over the past 20 years,” noted the other senior author, William B. Isaacs, PhD, professor of urology and oncology at the Johns Hopkins University School of Medicine in Baltimore, Maryland, in a statement. “It’s long been clear that prostate cancer can run in families, but pinpointing the underlying genetic basis has been challenging and previous studies have provided inconsistent results.”

The finding has implications for prostate cancer risk assessment and may provide new insights into the physical processes of this common disease.