title: Two percent of men with early-onset prostate cancer harbor germline mutations in the BRCA2 gene.
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.
authors.affiliation: Translational Cancer Genetics Team, Institute of Cancer Research, Sutton, Surrey, United Kingdom.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Edwards
authors.forename: Zsofia
authors.initials: Z
authors.lastname: Kote-Jarai
authors.forename: Julia
authors.initials: J
authors.lastname: Meitz
authors.forename: Rifat
authors.initials: R
authors.lastname: Hamoudi
authors.forename: Questa
authors.initials: Q
authors.lastname: Hope
authors.forename: Peter
authors.initials: P
authors.lastname: Osin
authors.forename: Rachel
authors.initials: R
authors.lastname: Jackson
authors.forename: Christine
authors.initials: C
authors.lastname: Southgate
authors.forename: Rashmi
authors.initials: R
authors.lastname: Singh
authors.forename: Alison
authors.initials: A
authors.lastname: Falconer
authors.forename: David P
authors.initials: DP
authors.lastname: Dearnaley
authors.forename: Audrey
authors.initials: A
authors.lastname: Ardern-Jones
authors.forename: Annette
authors.initials: A
authors.lastname: Murkin
authors.forename: Anna
authors.initials: A
authors.lastname: Dowe
authors.forename: Jo
authors.initials: J
authors.lastname: Kelly
authors.forename: Sue
authors.initials: S
authors.lastname: Williams
authors.forename: Richard
authors.initials: R
authors.lastname: Oram
authors.forename: Margaret
authors.initials: M
authors.lastname: Stevens
authors.forename: Dawn M
authors.initials: DM
authors.lastname: Teare
authors.forename: Bruce A J
authors.initials: BA
authors.lastname: Ponder
authors.forename: Simon A
authors.initials: SA
authors.lastname: Gayther
authors.forename: Doug F
authors.initials: DF
authors.lastname: Easton
authors.forename: Rosalind A
authors.initials: RA
authors.lastname: Eeles
mesh_terms: 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*