title: Prevalence of BRCA1 and BRCA2 germline mutations in young breast cancer patients: a population-based study.
abstract: Our aim was to estimate the prevalence of mutations in the BRCA1 and BRCA2 genes among unselected incident cases of breast cancer in young women. We identified 158 incident breast cancer cases diagnosed before age 46 years in predefined geographic areas in Girona and Tarragona, Spain, during 1995-1997. Of these, 136 (86%) provided information on family history of cancer and were screened for BRCA1 and BRCA2 mutations. Nine of the 136 (6.6%) were found to carry BRCA deleterious mutations (MUT) (1 BRCA1 and 8 BRCA2), and 20 were detected with rare BRCA variants of unknown significance (UV). Both MUT and US BRCA alterations were more frequent in younger patients: 7 (11.6%) MUT and 12 (19.3%) UV carriers were found in the group of 62 patients younger than 40 years, whereas 2 (2.7%) MUT and 9 (12%) US carriers were identified in the group of 74 patients aged 40-45. Family history of breast and ovarian cancers suggestive of hereditary condition (at least 2 first- or second-degree relatives affected with breast cancer or at least 1 relative affected with ovarian cancer or early-onset breast cancer) was absent for 5 of 9 MUT carriers. This suggests that BRCA screening policies based on family history of cancer would miss a considerable proportion of BRCA mutations. Mutations in the BRCA1 and BRCA2 genes explain at least 10% of breast cancer cases diagnosed before age 40 years. The contribution of these genes to early-onset breast cancer is likely to be even higher given that certain UV cases might be disease-associated.
authors.affiliation: Institut Català d'Oncologia, Hospitalet de LL, Barcelona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: de Sanjosé
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Léoné
authors.affiliation: Servei d'Oncologia, Hospital Universitari Sant Joan y Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Victoria
authors.initials: V
authors.lastname: Bérez
authors.affiliation: Unitat d'Epidemiologia i Registre del Càncer de Girona, Girona, Spain.
authors.forename: Angel
authors.initials: A
authors.lastname: Izquierdo
authors.affiliation: Institut Català d'Oncologia, Hospitalet de LL, Barcelona, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Font
authors.affiliation: Servei d'Oncologia, Hospital Universitari Sant Joan y Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Brunet
authors.affiliation: International Agency for Research on Cancer, Lyon, France.
authors.forename: Thierry
authors.initials: T
authors.lastname: Louat
authors.affiliation: Unitat d'Epidemiologia i Registre del Càncer de Girona, Girona, Spain.
authors.forename: Loreto
authors.initials: L
authors.lastname: Vilardell
authors.affiliation: Servei d'Oncologia, Hospital Universitari Sant Joan y Universitat Rovira i Virgili, Reus, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Borras
authors.affiliation: Unitat d'Epidemiologia i Registre del Càncer de Girona, Girona, Spain.
authors.forename: Pau
authors.initials: P
authors.lastname: Viladiu
authors.affiliation: Institut Català d'Oncologia, Hospitalet de LL, Barcelona, Spain.
authors.forename: F Xavier
authors.initials: FX
authors.lastname: Bosch
authors.affiliation: International Agency for Research on Cancer, Lyon, France.|Institut Gustave Roussy, Villejuif, France.
authors.forename: Gilbert M
authors.initials: GM
authors.lastname: Lenoir
authors.affiliation: International Agency for Research on Cancer, Lyon, France.|Laboratoire de Genetique, Hospices Civils de Lyon, Lyon, France.
authors.forename: Olga M
authors.initials: OM
authors.lastname: Sinilnikova
mesh_terms: D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D018095:Germ-Line Mutation / Q000235:genetics*; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D016133:Polymerase Chain Reaction; D011159:Population Surveillance; D015995:Prevalence; D012307:Risk Factors; D013030:Spain / Q000453:epidemiology
chemical_list: D004273:DNA, Neoplasm