BERKELEY, CA (UroToday.com) - For many men and women from families with hereditary colon, breast, and ovarian cancer, the ability to detect germline mutations associated with these cancers has transformed cancer screening. For example, having a mutation in BRCA1 increases the risk for breast cancer up to 60-fold. Therefore, mutation carriers should obtain magnetic resonance imaging-based screening and even consider prophylactic mastectomy. For prostate cancer, several germline mutations have been discovered, but none of them had a similar clinical utility. A study published in the New England Journal of Medicine in 2012 found that germline mutations in HOXB13 conferred a significantly increased risk of early-onset and hereditary prostate cancer.[1] However, the population studied was highly selected, including men with either familial or early-onset prostate cancer or who underwent prostatectomy for clinically localized prostate cancer at Johns Hopkins University. To better understand whether testing for this new mutation could have a role in everyday clinical practice, we examined the prevalence of the HOXB13 mutation in a real-life cohort of men scheduled to undergo prostate biopsy for clinical reasons.
We identified 948 men who had a DNA sample drawn prior to undergoing prostate biopsy. Only four of these men (0.42%) had the HOXB13 mutation. Among a subset of 301 patients with a family history positive for prostate cancer, none had the mutation. Three of the four men with the HOXB13 mutation did have cancer detected on biopsy, for a positive predictive value of 75%. Although this positive predictive value is fairly high, the fact that less than half a percent of patients presenting for prostate biopsy had the HOXB13 mutation limits the clinical utility of testing for this mutation in everyday practice.
Since the publication of our study, several other studies have confirmed both a low carrier rate and a significant association between HOXB13 and prostate cancer.[2, 3, 4] Taken together, these results imply that further examining how HOXB13 contributes to prostate cancer risk may help with our understanding of biological processes in familial prostate cancer. However, the low carrier rate in the general population questions the utility of testing for this mutation in everyday clinical practice.
References:
- Ewing CM, Ray AM, Lange EM, et al. Germline mutations in HOXB13 and prostate-cancer risk. N. Engl. J. Med. 2012; 366: 141–149.
- Akbari MR, Trachtenberg J, Lee J, et al. Association Between Germline HOXB13 G84E Mutation and Risk of Prostate Cancer. JNCI J Natl Cancer Inst 2012; 104: 1260–1262.
- Karlsson R, Aly M, Clements M, et al. A Population-based Assessment of Germline HOXB13 G84E Mutation and Prostate Cancer Risk. European Urology 2012; epub ahead of print.
- Stott-Miller M, Karyadi DM, Smith T, et al. HOXB13 mutations in a population-based, case-control study of prostate cancer. Prostate 2012; epub ahead of print.
Written by:
Florian R. Schroeck, MD, MS and John T. Wei, MD, MS as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Department of Urology, University of Michigan, Ann Arbor, MI USA
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