of the prevalence of germline mutations in BRCA1 and BRCA2 in women with
breast cancer diagnosed before thirty years of age or with a strong family
Dr Shirley Hodgson 1
To assess the prevalence of germline BRCA1 gene mutations in breast cancer patients with either early-onset sporadic disease or a family history of breast and/or ovarian cancer.
The majority of referrals to genetic family cancer clinics are of individuals with only a moderate family history of breast and/or ovarian cancer, and such referrals are increasing rapidly. Prioritisation of families for genetic testing, in the context of limited resources, is essential for the development of cost effective services. In order to assess the likely contribution of germline mutations in genes conferring a high risk of breast cancer in these referrals, we have ascertained two groups of women affected with breast cancer. The first is women affected at a young age, but with no known family history of breast/ovarian cancer, and the second a group of affected women with a limited family history of breast/ovarian cancer (with at least one breast cancer diagnosed below 45 years of age), characteristic of families currently referred.
Patients were ascertained from referrals to family cancer clinics in the Genetics Department at Guy's Hospital, the Royal Free Hospital, and St. Mary's Hospital, Manchester, and patients seen at the ICRF Breast Oncology Unit at Guy's Hospital.
345 unrelated patients with breast cancer
MAIN OUTCOME MEASURES
(i) Design of a sensitive, robust and
cost-effective strategy to screen breast cancer predisposition genes for mutations;
A mutation detection protocol was developed which uses multiplex
amplification of exons from genomic DNA and flourescent chemical cleavage
of mismatch to screen the entire coding sequence of the BRCA1 gene with
These findings suggest that patients with a modest family history of site specific breast cancer, or of breast and ovarian cancer, have a significant prevalence of germline mutations in the BRCA1 gene, whereas young sporadic patients are much less likely to have mutations. These findings have important implications for future mutation screening policy in early onset and familial breast cancer.
Ellis D., Greenman J., Izatt L., MacDermot K., Perrett C., Evans G.,
Hodgson S., and Mathew C. (1998) Rapid mutation screening of the BRCA1
gene in early onset sporadic and familial breast cancer patients using
chemical cleavage of mismatch analysis (Abstract 02.38, British Human
Genetics Conference, 28-30.9.98, York). J Med Genet 35 (suppl 1), S43.
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