FOUNDER BRCA1 AND BRCA2 MUTATIONS IN FRENCH-CANADIAN BREAST AND OVARIAN-CANCER FAMILIES

We have identified four mutations in each of the breast cancer-suscept ibility genes, BRCA1 and BRCA2, in French Canadian breast cancer and b reast/ovarian cancer families from Quebec. To identify founder effects , we examined independently ascertained French Canadian cancer familie s for the distribution of these eight mutations. Mutations were found in 41 of 97 families. Six of eight mutations were observed at least tw ice. The BRCA1 C4446T mutation was the most common mutation found, fol lowed by the BRCA2 8765delAG mutation. Together, these mutations were found in 28 of 41 families identified to have a mutation. The odds of detection of any of the four BRCA1 mutations was 18.7 x greater if one or more cases of ovarian cancer were also present in the family. The odds of detection of any of the four BRCA2 mutations was 5.3 x greater if there were at least five cases of breast cancer in the family. Int erestingly, the presence of a breast cancer case <36 years of age was strongly predictive of the presence of any of the eight mutations scre ened. Carriers of the same mutation, from different families, shared s imilar haplotypes, indicating that the mutant alleles were likely to b e identical by descent for a mutation in the founder population. The i dentification of common BRCA1 and BRCA2 mutations will facilitate carr ier detection in French Canadian breast cancer and breast/ovarian canc er families.