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Genes With Potential Clinical Relevance in Prostate Cancer Risk

Table 3. Case-Control Studies in Ashkenazi Jewish Populations ofBRCA1andBRCA2and Prostate Cancer Risk continued...

These studies support the hypothesis that prostate cancer occurs excessively among carriers of AJ founder mutations and suggest that the risk may be greater among men with the BRCA2 founder mutation (6174delT) than among those with one of the BRCA1 founder mutations (185delAG; 5382insC). The magnitude of the BRCA2-associated risks differ somewhat, undoubtedly because of interstudy differences related to participant ascertainment, calendar time differences in diagnosis, and analytic methods. Some data suggest that BRCA-related prostate cancer has a significantly worse prognosis than prostate cancer that occurs among noncarriers.[16]

Other populations

The association between prostate cancer and mutations in BRCA1 and BRCA2 has also been studied in other populations.

Three Polish BRCA1 founder mutations (C16G, 4153delA, and 5382insC) were studied in 1,793 Polish prostate cancer cases and 4,570 controls. Overall, the prevalence of the three mutations combined was identical in cases and controls. However, the most common mutation, 5382insC, occurred in 0.06% of cases versus 0.37% of controls, suggesting that this specific variant is not likely to be associated with increased prostate cancer risk. Furthermore, the presence of either of the other two mutations (C16G and 4153delA) was associated with a 3.6-fold increase in prostate cancer risk (P = .045) and an even greater risk (OR, 12; P = .0004) of familial prostate cancer. These data suggest that prostate cancer risk in BRCA1 mutation carriers varies with the location of the mutation (i.e., there is a correlation between genotype and phenotype).[17] This observation might explain some of the inconsistencies encountered in prior studies of this association, since populations may have varied relative to the proportion of persons with specific pathogenic BRCA1 mutations.

Several case series have also explored the role of BRCA1 and BRCA2 mutations and prostate cancer risk.


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