Faulty BRCA1 Increases Risk of Prostate Cancer

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(ChemotherapyAdvisor) – Men who inherit a faulty BRCA1 gene have four times the risk of developing prostate cancer than the general population, according to a multinational team of researchers, including those at the Institute of Cancer Research, Sutton, UK, and The Royal Marsden NHS Foundation Trust, Sutton, UK. The article, entitled “Germline BRCA1 Mutations Increase Prostate Cancer Risk,” was published online in the British Journal of Cancer on April 19.

Previously published reports have demonstrated an increased risk of prostate cancer in male BRCA1 mutation carriers in family studies of breast cancer. However, according the study's authors, “there is a controversy as to whether this risk is substantiated.” So the purpose of this study was to evaluate the role of germline BRCA1 mutations in prostate cancer predisposition by performing a candidate gene study in a large U.K. population sample set.

The researchers screened 913 cases aged 36–86 years for germline BRCA1 mutation. Genomic methods were then used to analyze the entire coding region of the BRCA1 gene and assess the frequency of large rearrangements in 460 cases.

The researchers identified four deleterious mutations and 45 unclassified variants in the BRCA1 coding sequence. “The frequency of deleterious BRCA1 mutation in this study is 0.45%; 3 of the mutation carriers were affected at age ≤65 years and one developed prostate cancer at 69 years. Using previously estimated population carrier frequencies, deleterious BRCA1 mutations confer a relative risk of prostate cancer of approximately 3.75-fold (95% confidence interval 1.02–9.6), translating to a 8.6% cumulative risk by age 65.”

The authors concluded: “This study shows evidence for an increased risk of prostate cancer in men who harbor germline mutations in BRCA1. This could have a significant impact on possible screening strategies and targeted treatments.”

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