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PMID: 9792861 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Founder BRCA1 and BRCA2 mutations in French Canadian breast and ovarian cancer families.

American journal of human genetics ·Vol. 63 ·No. 5 ·1998-11-00 ·Pages 1341-51

Tonin PN, Mes-Masson AM, Futreal PA, Morgan K, Mahon M, Foulkes WD, Cole DE, Provencher D, Ghadirian P, Narod SA

Abstract

We have identified four mutations in each of the breast cancer-susceptibility genes, BRCA1 and BRCA2, in French Canadian breast cancer and breast/ovarian cancer families from Quebec. To identify founder effects, we examined independently ascertained French Canadian cancer families for the distribution of these eight mutations. Mutations were found in 41 of 97 families. Six of eight mutations were observed at least twice. The BRCA1 C4446T mutation was the most common mutation found, followed 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 18.7x 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 5.3x greater if there were at least five cases of breast cancer in the family. Interestingly, the presence of a breast cancer case <36 years of age was strongly predictive of the presence of any of the eight mutations screened. Carriers of the same mutation, from different families, shared similar haplotypes, indicating that the mutant alleles were likely to be identical by descent for a mutation in the founder population. The identification of common BRCA1 and BRCA2 mutations will facilitate carrier detection in French Canadian breast cancer and breast/ovarian cancer families.

MeSH Terms
BRCA1 Protein/genetics BRCA2 Protein Breast Neoplasms/genetics Canada DNA Primers Family Female France/ethnology Genes, BRCA1 Genes, Tumor Suppressor Genetic Markers Humans Middle Aged Neoplasm Proteins/genetics Neoplasms, Second Primary/genetics Ovarian Neoplasms/genetics Point Mutation Polymerase Chain Reaction Sequence Deletion Transcription Factors/genetics
Chemicals
BRCA1 Protein BRCA2 Protein DNA Primers Genetic Markers Neoplasm Proteins Transcription Factors
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Tonin P N
Departments of Human Genetics and Medicine, Division of Medical Genetics, McGill University, Montreal, Quebec, Canada. tonin@medcor.mcgill.ca
Mes-Masson A M
Futreal P A
Morgan K
Mahon M
Foulkes W D
Cole D E
Provencher D
Ghadirian P
Narod S A
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/302099
Email
tonin@medcor.mcgill.ca
Published
1998-11-00
Pages
1341-51
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1377544
Subset
IM
External Links
PubMed source DOI: 10.1086/302099 PMC Full Text View journal details
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