BREAST AND OVARIAN-CANCER INCIDENCE IN BRCAI-MUTATION CARRIERS

Dominant predisposition to early-onset breast cancer and/or ovarian ca ncer in many families is known to be the result of germ-line mutations in a gene on chromosome 17q, known as BRCA1, In this paper we use dat a from families with evidence of linkage to BRCA1 to estimate the age- specific risks of breast and ovarian cancer in BRCA1-mutation carriers and to examine the variation in risk between and within families, Und er the assumption of no heterogeneity of risk between families, BRCA1 is estimated to confer a breast cancer risk of 54% by age 60 years (95 % confidence interval [CI] 27%-71%) and an ovarian cancer risk of 30% by age 60 years (95% CI 8%-47%). Similar lifetime-risk estimates are o btained by examining the risks of contralateral breast cancer and of o varian cancer, in breast cancer cases in linked families. However, the re is significant evidence of heterogeneity of risk between families; a much better fit to the data is obtained by assuming two BRCA1 allele s, one conferring a breast cancer risk of 62% and an ovarian cancer ri sk of 11% by age 60 years, the other conferring a breast cancer risk o f 39% and an ovarian cancer risk of 42%, with the first allele represe nting 71% of all mutations (95% CI 55%-87%), There is no evidence of c lustering of breast and ovarian cancer cases within families.