Significant proportion of breast and/or ovarian cancer families of french Canadian descent harbor 1 of 5 BRCA1 and BRCA2 mutations

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 I 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. (C) 2004 Wiley-Liss. Inc.