title: BRCA2 mutations in 154 finnish male breast cancer patients.
abstract: The etiology and pathogenesis of male breast cancer (MBC) are poorly known. This is due to the fact that the disease is rare, and large-scale genetic epidemiologic studies have been difficult to carry out. Here, we studied the frequency of eight recurrent Finnish BRCA2 founder mutations in a large cohort of 154 MBC patients (65% diagnosed in Finland from 1967 to 1996). Founder mutations were detected in 10 patients (6.5%), eight of whom carried the 9346(-2) A>G mutation. Two novel mutations (4075 delGT and 5808 del5) were discovered in a screening of the entire BRCA2 coding region in 34 samples. However, these mutations were not found in the rest of the 120 patients studied. Patients with positive family history of breast and/or ovarian cancer were often BRCA2 mutation carriers (44%), whereas those with no family history showed a low frequency of involvement (3.6%; P < .0001). Finally, we found only one Finnish MBC patient with 999 del5, the most common founder mutation in Finnish female breast cancer (FBC) patients, and one that explains most of the hereditary FBC and MBC cases in Iceland. The variation in BRCA2 mutation spectrum between Finnish MBC patients and FBC patients in Finland and breast cancer patients in Iceland suggests that modifying genetic and environmental factors may significantly influence the penetrance of MBC and FBC in individuals carrying germline BRCA2 mutations in some populations.
authors.affiliation: Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere, Tampere University Hospital, Tampere, Finland.
authors.forename: Kirsi
authors.initials: K
authors.lastname: Syrjäkoski
authors.forename: Tuula
authors.initials: T
authors.lastname: Kuukasjärvi
authors.forename: Kati
authors.initials: K
authors.lastname: Waltering
authors.forename: Karin
authors.initials: K
authors.lastname: Haraldsson
authors.forename: Anssi
authors.initials: A
authors.lastname: Auvinen
authors.forename: Ake
authors.initials: A
authors.lastname: Borg
authors.forename: Tommi
authors.initials: T
authors.lastname: Kainu
authors.forename: Olli-P
authors.initials: OP
authors.lastname: Kallioniemi
authors.forename: Pasi A
authors.initials: PA
authors.lastname: Koivisto
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018567:Breast Neoplasms, Male / Q000208:ethnology / Q000235:genetics*; D005387:Finland; D018703:Founder Effect; D005787:Gene Frequency / Q000235:genetics; D024522:Genes, BRCA2; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*