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

ABSTRACT: 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.

SUBMITTER: Schroeck FR

PROVIDER: S-EPMC4193792 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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

Schroeck Florian R FR Zuhlke Kimberly A KA Siddiqui Javed J Siddiqui Rabia R Cooney Kathleen A KA Wei John T JT

The Journal of urology 20121002 3

<h4>Purpose</h4>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.<h4>Materials and methods</h4>We prospectively collected clinical information and DNA samples from men who underwent diagnostic prostate biopsy between June 2005 and October 2011. We genotyp ...[more]

PMID: 23036981

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Project description:BackgroundThe homeobox B13 (HOXB13) G84E mutation has been recommended for use in genetic counselling for prostate cancer (PCa), but the magnitude of PCa risk conferred by this mutation is uncertain.ObjectiveTo obtain precise risk estimates for mutation carriers and information on how these vary by family history and other factors.Design, setting, and participantsTwo-fold: a systematic review and meta-analysis of published risk estimates, and a kin-cohort study comprising pedigree data on 11983 PCa patients enrolled during 1993-2014 from 189 UK hospitals and who had been genotyped for HOXB13 G84E.Outcome measurements and statistical analysisRelative and absolute PCa risks. Complex segregation analysis with ascertainment adjustment to derive age-specific risks applicable to the population, and to investigate how these vary by family history and birth cohort.Results and limitationsA meta-analysis of case-control studies revealed significant heterogeneity between reported relative risks (RRs; range: 0.95-33.0, p<0.001) and differences by case selection (p=0.007). Based on case-control studies unselected for PCa family history, the pooled RR estimate was 3.43 (95% confidence interval [CI] 2.78-4.23). In the kin-cohort study, PCa risk for mutation carriers varied by family history (p<0.001). There was a suggestion that RRs decrease with age, but this was not significant (p=0.068). We found higher RR estimates for men from more recent birth cohorts (p=0.004): 3.09 (95% CI 2.03-4.71) for men born in 1929 or earlier and 5.96 (95% CI 4.01-8.88) for men born in 1930 or later. The absolute PCa risk by age 85 for a male HOXB13 G84E carrier varied from 60% for those with no PCa family history to 98% for those with two relatives diagnosed at young ages, compared with an average risk of 15% for noncarriers. Limitations include the reliance on self-reported cancer family history.ConclusionsPCa risks for HOXB13 G84E mutation carriers are heterogeneous. Counselling should not be based on average risk estimates but on age-specific absolute risk estimates tailored to individual mutation carriers' family history and birth cohort.Patient summaryMen who carry a hereditary mutation in the homeobox B13 (HOXB13) gene have a higher than average risk for developing prostate cancer. In our study, we examined a large number of families of men with prostate cancer recruited across UK hospitals, to assess what other factors may contribute to this risk and to assess whether we could create a precise model to help in predicting a man's prostate cancer risk. We found that the risk of developing prostate cancer in men who carry this genetic mutation is also affected by a family history of prostate cancer and their year of birth. This information can be used to assess more personalised prostate cancer risks to men who carry HOXB13 mutations and hence better counsel them on more personalised risk management options, such as tailoring prostate cancer screening frequency.

Dataset Information

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

Publications

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

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