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Am J Hum Genet. 2003 Jan;72(1):1-12. Epub 2002 Dec 9.

Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene.

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  • 1Translational Cancer Genetics Team, Institute of Cancer Research, Sutton, Surrey, United Kingdom.

Abstract

Studies of families with breast cancer have indicated that male carriers of BRCA2 mutations are at increased risk of prostate cancer, particularly at an early age. To evaluate the contribution of BRCA2 mutations to early-onset prostate cancer, we screened the complete coding sequence of BRCA2 for germline mutations, in 263 men with diagnoses of prostate cancer who were </=55 years of age. Protein-truncating mutations were found in six men (2.3%; 95% confidence interval 0.8%-5.0%), and all of these mutations were clustered outside the ovarian-cancer cluster region. The relative risk of developing prostate cancer by age 56 years from a deleterious germline BRCA2 mutation was 23-fold. Four of the patients with mutations did not have a family history of breast or ovarian cancer. Twenty-two variants of uncertain significance were also identified. These results confirm that BRCA2 is a high-risk prostate-cancer-susceptibility gene and have potential implications for the management of early-onset prostate cancer, in both patients and their relatives.

PMID:
12474142
[PubMed - indexed for MEDLINE]
PMCID:
PMC420008
Free PMC Article

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