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Genetics of Prostate Cancer (PDQ®): Genetics - Health Professional Information [NCI] - Genes With Potential Clinical Relevance in Prostate Cancer Risk

While genetic testing for prostate cancer is not yet standard clinical practice, research from selected cohorts has reported that prostate cancer risk is elevated in men with mutations in BRCA1, BRCA2, and on a smaller scale, in mismatch repair (MMR) genes. Since clinical genetic testing is available for these genes, information about risk of prostate cancer based on alterations in these genes is included in this section. In addition, mutations in HOXB13 were reported to account for a proportion of hereditary prostate cancer. Although clinical testing is not yet available for HOXB13 alterations, it is expected that this gene will have clinical relevance in the future and therefore is also included in this section. The genetic alterations described in this section require further study and are not to be used in routine clinical practice at this time.


Studies of male BRCA1[1] and BRCA2 mutation carriers demonstrate that these individuals have a higher risk of prostate cancer and other cancers.[2]

BRCAmutation–associated prostate cancer risk

The risk of prostate cancer in BRCA mutation carriers has been studied in various settings.

In an effort to clarify the relationship between BRCA mutations and prostate cancer risk, findings from several case series are summarized in Table 2.

Table 2. Case Series ofBRCAMutations in Prostate Cancer

StudyPopulationProstate Cancer Risk (BRCA1)Prostate Cancer Risk (BRCA2)
BCLC = Breast Cancer Linkage Consortium; CI = confidence interval; OCCR = Ovarian Cancer Cluster Region; RR = relative risk.
a Includes all cancers except breast, ovarian, and nonmelanoma skin cancers.
BCLC, 1999[3]BCLC family set that included 173BRCA2linkage or mutation-positive families, among which there were 3,728 individuals and 333 cancersaNot assessedOverall: RR, 4.65 (95% CI, 3.48–6.22)
Men <65 y: RR, 7.33 (95% CI, 4.66–11.52)
Thompson et al., 2001[4]BCLC family set that included 164BRCA2mutation-positive families, among which there were 3,728 individuals and 333 cancersaNot assessedOCCR: RR, 0.52 (95% CI, 0.24–1.00)
Thompson et al., 2002[1]BCLC family set that included 7,106 women and 4,741 men, among which 2,245 wereBRCA1mutation carriers, 1,106 were tested noncarriers, and 8,496 were not tested for mutationsOverall: RR, 1.07 (95% CI, 0.75–1.54)Not assessed
Men <65 y: RR, 1.82 (95% CI, 1.01–3.29)

A review of the relationship between germline mutations in BRCA2 and prostate cancer risk supports the view that this gene confers a significant increase in risk among male members of hereditary breast and ovarian cancer families but that it likely plays only a small role, if any, in site-specific, multiple-case prostate cancer families.[5]

Prevalence ofBRCAfounder mutations in men with prostate cancer

Ashkenazi Jewish

Several studies in Israel and in North America have analyzed the frequency of BRCAfounder mutations among Ashkenazi men with prostate cancer.[6,7,8] Two specific BRCA1 mutations (185delAG and 5382insC) and one BRCA2 mutation (6174delT) are common in individuals of Ashkenazi Jewish (AJ) ancestry. Carrier frequencies for these mutations in the general Jewish population are 0.9% (95% CI, 0.7–1.1) for the 185delAG mutation, 0.3% (95% CI, 0.2–0.4) for the 5382insC mutation, and 1.3% (95% CI, 1.0–1.5) for the BRCA2 6174delT mutation.[9,10,11,12] (Refer to the High-Penetrance Breast and/or Ovarian Cancer Susceptibility Genes section in the PDQ summary on Genetics of Breast and Ovarian Cancer for more information about BRCA1 and BRCA2 genes.) In these studies, the RRs were commonly greater than 1, but only a few have been statistically significant. Many of these studies were not sufficiently powered to rule out a lower, but clinically significant, risk of prostate cancer in carriers of Ashkenazi BRCA founder mutations.


WebMD Public Information from the National Cancer Institute

Last Updated: February 25, 2014
This information is not intended to replace the advice of a doctor. Healthwise disclaims any liability for the decisions you make based on this information.
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