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 green 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 ovarian cancer risk before age 50 is 0.4% (95% confidence interval 0%-1%), and 27% (95% CI 0%-47%) by age 70 years.
The pink, yellow, and blue curves represent the ovarian cancer risks for the BRCA2 mutation families, according to mutation location. The gene has been divided into three regions: (1) Exons 1-10 and 11, nucleotides 1-1034; (2) Exon 11, nucleotides 1035-6629; (3) Exon 11, nucleotides 6630-end, and exons 12-23. The middle region corresponds to the ovarian cancer-cluster region (OCCR) suggested by Gayther et al. (1997). The results suggest a genotype-phenotype correlation in that the estimated ovarian cancer risks are higher in the OCCR, in agreement with the results of Gayther et al. (1997) obtained in 25 families with multiple cases of breast and/or ovarian cancer ascertained in the United Kingdom and Eire. However, the confidence limits are very wide: the cumulative ovarian cancer risk before age 60 is 24% (95% CI 0%-64%), and 76% (95% CI 0%-98%) by age 70 years. The estimated breast cancer risks appear to be similar in all three groups (not shown). The breast cancer risks in the OCCR are shown for comparison (orange curve).