The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case-control-family study.
Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries.
Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls.
Full manual sequencing of the coding region of BRCA 1 was conducted in a randomly stratified sample of 91 cases ; 47 with, and 44 without, a family history of breast cancer in a first-or second-degree relative.
All detected variants were tested in a random sample of 67 controls.
Three cases with a (protein-truncating) mutation were detected.
Only one case had a family history ; her mother had breast cancer, but did not carry the mutation.
The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA 1 was estimated to be 3.8% (95% Cl 0.3-12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility.
Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence.
Mots-clés Pascal : Tumeur maligne, Glande mammaire, Mutation, Gène suppresseur tumeur, Variant génétique, Prévalence, Epidémiologie, Australie, Océanie, Etude familiale, Etude cas témoin, Homme, Glande mammaire pathologie, Génétique, Gène BRCA1
Mots-clés Pascal anglais : Malignant tumor, Mammary gland, Mutation, Tumor suppressor gene, Genetic variant, Prevalence, Epidemiology, Australia, Oceania, Family study, Case control study, Human, Mammary gland diseases, Genetics
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 99-0047164
Code Inist : 002B20E02. Création : 31/05/1999.