Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene.
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.
Edwards
Stephen M
SM
Translational Cancer Genetics Team, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
Kote-Jarai
Zsofia
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Meitz
Julia
J
Hamoudi
Rifat
R
Hope
Questa
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Osin
Peter
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Jackson
Rachel
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Southgate
Christine
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Singh
Rashmi
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Falconer
Alison
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Dearnaley
David P
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Ardern-Jones
Audrey
A
Murkin
Annette
A
Dowe
Anna
A
Kelly
Jo
J
Williams
Sue
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Oram
Richard
R
Stevens
Margaret
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Teare
Dawn M
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Ponder
Bruce A J
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Gayther
Simon A
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Easton
Doug F
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Eeles
Rosalind A
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D000328:Adult; D017668:Age of Onset; D000368:Aged; D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics; D010375:Pedigree; D011110:Polymorphism, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics*