title: [The limited spectrum of pathogenic BRCA1 and BRCA2 mutations in the French Canadian breast and breast-ovarian cancer families, a founder population of Quebec, Canada].
abstract: The unique genetic demography of the French Canadian population of Quebec, Canada, has provided a means to study the contribution of BRCA1 and BRCA2, the breast-ovarian cancer susceptibility genes. Here we review BRCA1 and BRCA2 in the context of French Canadian cancer families, a well-characterized founder population known for its contributions to medical genetics. Pathogenic BRCA1 and BRCA2 mutations contribute to a significant proportion of hereditary breast and/or ovarian cancer families of French Canadian descent. BRCA1 and BRCA2 mutations have been reported in approximately 40 % of families with at least three cases of breast and/or ovarian cancer, where breast cancer diagnosis occurred before age 66 years, and where all cases occurred within first-, second- and/or third-degree relatives to index affected cases tested for mutations. The proportion of mutation-positive families was very similar to that reported in independent studies of families not selected for ethnicity. However, 84 % of mutation-positive families were accounted for by one of eight pathogenic mutations in BRCA1 (2953delGTA + C, 3875delGTCT, and 4446C --> T) and BRCA2 (2816insA, 3398delAAAAG, 6085G --> T, 6503delTT, and 8765delAG). Haplotype analyses has suggested that carriers of the most common recurring mutations share a related ancestry. This effect has been attributed to common founders in the French Canadian population of Quebec who emigrated from France in between 1608 and 1759. It is possible that novel highly penetrant cancer susceptibility genes account for a fraction of the 60 % of BRCA mutation-negative French Canadian cancer families. The continued genetic analysis and phenotypic characterization of French Canadian cancer families is warranted given the large family structure of these families are amenable for classical genome-wide linkage analysis for novel breast and ovarian cancer susceptibility genes.
authors.affiliation: Department of Medicine, McGill University, and The Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada. patricia.tonin@mcgill.ca
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tonin
mesh_terms: D000367:Age Factors; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics*; D004641:Emigration and Immigration; D005190:Family; D005260:Female; D018703:Founder Effect; D005602:France / Q000208:ethnology; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation / Q000235:genetics; D006801:Humans; D009154:Mutation / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000208:ethnology / Q000235:genetics*; D011792:Quebec