Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
, 7, 23

Haplotype Analysis Suggest Common Founders in Carriers of the Recurrent BRCA2 Mutation, 3398delAAAAG, in French Canadian Hereditary Breast and/Ovarian Cancer Families

Affiliations

Haplotype Analysis Suggest Common Founders in Carriers of the Recurrent BRCA2 Mutation, 3398delAAAAG, in French Canadian Hereditary Breast and/Ovarian Cancer Families

Kathleen K Oros et al. BMC Med Genet.

Abstract

Background: The 3398delAAAAG mutation in BRCA2 was recently found to recur in breast and/or ovarian cancer families from the French Canadian population of Quebec, a population that has genetic attributes consistent with a founder effect. To characterize the contribution of this mutation in this population, this study established the frequency of this mutation in breast and ovarian cancer cases unselected for family history of cancer, and determined if mutation carriers shared a common ancestry.

Methods: The frequency was estimated by assaying the mutation in series of French Canadian breast cancer cases diagnosed before age 41 (n = 60) or 80 (n = 127) years of age, and ovarian cancer cases (n = 80) unselected for family history of cancer by mutation analysis. Haplotype analysis was performed to determine if mutation carriers shared a common ancestry. Members from 11 families were analyzed using six polymorphic microsatellite markers (cen-D13S260-D13S1699-D13S1698-D13S1697-D13S1701-D13S171-tel) spanning approximately a 3.6 cM interval at the chromosomal region 13q13.1, which contains BRCA2. Allele frequencies were estimated by genotyping 47 unaffected female individuals derived from the same population. Haplotype reconstruction of unaffected individuals was performed using the program PHASE.

Results: The recurrent BRCA2 mutation occurred in 1 of 60 (1.7%) women diagnosed with breast cancer before 41 years of age and one of 80 (1.3%) women with ovarian cancer. No mutation carriers were identified in the series of breast cancer cases diagnosed before age 80. Mutation carriers harboured one of two haplotypes, 7-3-9-3 - [3/4]-7, that varied with marker D13S1701 and which occurred at a frequency of 0.001. The genetic analysis of D13S1695, a polymorphic marker located approximately 0.3 cM distal to D13S171, did not favour a genetic recombination event to account for the differences in D13S1701 alleles within the haplotype. Although mutation carriers harbour genotypes that are frequent in the French Canadian population, neither mutation-associated haplotype was plausible in reconstructed haplotypes of 47 individuals of French Canadian descent.

Conclusion: These results suggest that mutation carriers share a related ancestry; further supporting the concept that recurrent BRCA1 and BRCA2 mutations in the French Canadian population could be attributed to common founders. This finding provides further support for targeted screening of recurrent mutations in this population before large-scale mutation analyses are performed.

Similar articles

See all similar articles

Cited by 8 PubMed Central articles

See all "Cited by" articles

References

    1. Tonin PN, Mes-Masson AM, Futreal PA, Morgan K, Mahon M, Foulkes WD, Cole DE, Provencher D, Ghadirian P, Narod SA. Founder BRCA1 and BRCA2 mutations in French Canadian breast and ovarian cancer families. Am J Hum Genet. 1998;63:1341–1351. doi: 10.1086/302099. - DOI - PMC - PubMed
    1. Claus EB, Schildkraut JM, Thompson WD, Risch NJ. The genetic attributable risk of breast and ovarian cancer. Cancer. 1996;77:2318–2324. doi: 10.1002/(SICI)1097-0142(19960601)77:11<2318::AID-CNCR21>3.0.CO;2-Z. - DOI - PubMed
    1. Ford D, Easton DF, Bishop DT, Narod SA, Goldgar DE. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet. 1994;343:692–695. doi: 10.1016/S0140-6736(94)91578-4. - DOI - PubMed
    1. Ford D, Easton DF, Stratton M, Narod S, Goldgar D, Devilee P, Bishop DT, Weber B, Lenoir G, Chang-Claude J, et al. Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1998;62:676–689. doi: 10.1086/301749. - DOI - PMC - PubMed
    1. Hopper JL, Southey MC, Dite GS, Jolley DJ, Giles GG, McCredie MR, Easton DF, Venter DJ. Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study. Cancer Epidemiol Biomarkers Prev. 1999;8:741–747. - PubMed

Publication types

Feedback