Germ-line BRCA1 mutations in selected men with prostate cancer.

Prostate cancer is the most common malignancy among American men. Although the causes of prostate cancer are unknown, a family history of the disease is one of the strongest risk factors identified, to date. Men with an affected first-degree relative with prostate cancer have at least a two-to-three-fold-higher risk of developing the disease compared with men who have no such family history. Epidemiological observations also suggest a clustering of prostate and breast cancers in some families. More specifically, at least two studies suggest that inherited mutations in highly penetrant dominant genes such as BRCA1, which predisposes women to breast and ovarian cancers, may also be associated with an increased risk of prostate cancer in men. In a study of seven large Icelandic breast cancer families, two of which showed evidence of linkage to BRCA1, prostate cancer was found to be the second most frequent malignancy after breast cancer. Among presumed paternal carriers of mutant breast cancer gene alleles, 44% had a history of prostate cancer. Additional evidence regarding BRCA1 and prostate cancer risk comes from an analysis of 33 BRCA1-linked families. This cooperative study estimated a relative risk of prostate cancer of 3.33 (95% confidence interval 1.8-6.2) among men carryingmore » mutations compared with the general population. 26 refs., 3 tabs.« less

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