BRCA1 MUTATIONS IN SOUTHERN ENGLAND

If genetic testing for breast and ovarian cancer predisposition is to become available within a public health care system there needs to be a rational and cost-effective approach to mutation analysis. We have s creened for BRCA1 mutations in 230 women with breast cancer, all from the Wessex region of southern England, in order to establish the param eters on which to base a cost-effective regional mutation analysis str ategy. Truncating mutations were detected in 10/155 (6.5%) consecutive cases selected only for diagnosis under the age of 40 (nine of these ten women had a strong family history of breast or ovarian cancer), 3/ 61 (4.9%) bilateral-breast cancer cases (all three mutations occurring among women for whom the first cancer was diagnosed under 40 years) a nd 8/30 (26.6%) breast cancer cases presenting to the genetics clinic (for whom a strong family history of breast acid/or ovarian cancer was present). Ten different mutations were detected in 17 families, but t hree of these accounted for 10/17 (59%) of the families. The cost of s creening the population for mutations in the entire BRCA1 gene is unac ceptably high. However, the cost of screening a carefully selected pat ient cohort is low, the risk of misinterpretation much less and the po tential clinical benefits clearer.