title: Significant proportion of breast and/or ovarian cancer families of French Canadian descent harbor 1 of 5 BRCA1 and BRCA2 mutations.
abstract: In 1998, we reported that a significant proportion of breast and/or ovarian cancer families of French Canadian descent harbor specific germline mutations in BRCA1 or BRCA2 attributed to common founders. Here we report the frequency of previously described mutations (n = 7) and 13 mutations identified in French Canadian families since 1998, in a new group of families (n = 88). Four of the previously described mutations, 4446C>T, 2953delGTAinsC, 8765delAG and 6085C>T, account for 72% and 69% of mutation-positive families in previously (n = 81) and recently ascertained groups, respectively. Only 2 of 13 recently identified mutations were found in more than 1 family: 3875delGTCT (n = 2) and 3398delAAAAG (n = 4). The 2 groups (ascertained pre- and post-gene discovery) did not differ significantly when distribution of mutations based on cancer syndrome phenotype and age of diagnosis or number of breast cancer cases were compared. Five common mutations accounted for a significant proportion (84%) of all mutation-positive families. The age of diagnosis of female breast cancer in mutation-negative families was significantly higher than that of the mutation-positive families (p<0.0001). The total number of cases of cancer per family was significantly lower in mutation-negative than mutation-positive families (p<0.001). Our results define a new mutation panel for screening BRCA1/2 mutations and the phenotype of mutation-positive families harboring the common mutations in the French Canadian population.
authors.affiliation: Department of Human Genetics, McGill University, Montreal, Canada.
authors.forename: Kathleen K
authors.initials: KK
authors.lastname: Oros
authors.forename: Parviz
authors.initials: P
authors.lastname: Ghadirian
authors.forename: Celia M T
authors.initials: CM
authors.lastname: Greenwood
authors.forename: Chantal
authors.initials: C
authors.lastname: Perret
authors.forename: Zhen
authors.initials: Z
authors.lastname: Shen
authors.forename: Yosabeth
authors.initials: Y
authors.lastname: Paredes
authors.forename: Suzanna L
authors.initials: SL
authors.lastname: Arcand
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
authors.forename: Steven A
authors.initials: SA
authors.lastname: Narod
authors.forename: William D
authors.initials: WD
authors.lastname: Foulkes
authors.forename: Diane
authors.initials: D
authors.lastname: Provencher
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tonin
mesh_terms: D000328:Adult; D000368:Aged; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D002170:Canada; D005190:Family; D005260:Female; D005602:France; D005787:Gene Frequency; D018095:Germ-Line Mutation; D006801:Humans; D008297:Male; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000175:diagnosis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*
chemical_list: D019313:BRCA1 Protein; D024682:BRCA2 Protein