Taken from Ford et al. (1998). Data from 32 families in which a BRCA2 mutation was found and in which D13S267 typing was available and informative. Each family contained at least 4 cases of either female breast cancer diagnosed at age <60 years or male breast cancer diagnosed at any age, irrespective of any ovarian cancer in the family.
The blue curve represents estimations of the overall penetrance of BRCA2 obtained by maximizing the LOD score with respect to different penetrance functions. This is equivalent to maximizing the likelihood of the marker data, conditional on all the disease phenotype data and allows the penetrance to be estimated free of bias due to ascertainment of families on the basis of multiple affected individuals. The cumulative risk before age 50 is 29% (95% confidence interval 9%-44%), and 88% (95% CI 48%-97%) by age 70 years.
The yellow curve shows the risks obtained for BRCA2 mutation carriers if the 82 families with at least 6 cases of breast cancer (females at age <60 years or males at any age) are attributed to BRCA1 or BRCA2. The risks by age 70 are very similar in the two analyses, and even though the estimated breast cancer risks are higher in the 40-59 years age group than in the mutation families, this difference is not significant (by age 50: P=0.11; by age 60: P=0.50).