Family History

Men with a brother or father with prostate cancer have twice the risk for prostate cancer compared to the rest of the population.5 There appears to be a familial clustering of a prostate cancer syndrome and genome-wide scans have identified potential prostate cancer susceptibility candidate genes. Male carriers of germline mutations of BRCA1 and BRCA2 are known to have an increased risk for developing prostate cancer.6 Common exposure to environmental and other risk factors may also contribute to increased risk among patients with first degree relatives with prostate cancer.5,7

An alternative explanation for the familial clustering may be polymorphisms in genes important for prostate cancer function and development.5, Candidate polymorphisms include a polymorphism in the androgen receptor, which has two different nucleotide repeat variants, the CAG or the GCC. The CAG repeat varies in repeat number from 11 to 31 repeats in healthy individuals, and the number of repeats is inversely proportional to the activity of the androgen receptor. Some studies have demonstrated that shorter CAG repeats are associated with increased prostate cancer risk. Another candidate polymorphism is SRD5A2, which is the gene that codes for 5-a-reductase, the enzyme that converts testosterone to the more active DHT. A variant in SRD5A2, the Ala49Thr, increases the activity and may increase prostate cancer risk.5,7

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