THE KIN-COHORT STUDY FOR ESTIMATING PENETRANCE

A cross-sectional study may be more feasible than a cohort or case-con trol study for examining the effect of a genetic mutation on cancer pe netrance outside of cancer families. The kin-cohort design uses Volunt eer probands selected from a population with a relatively high frequen cy of the mutations of interest. By considering the cancer risk in fir st-degree relatives of mutation-positive and -negative probands as a w eighted average of the risk in carriers and noncarriers, with weights calculated assuming a known mode of inheritance, one can infer the pen etrance of the mutations. The estimates of penetrance by age 70 years for three specific mutations in the BRCA1 and BRCA2 genes common among Ashkenazi Jews for the first occurrence of breast or ovary cancer is 63%. The kin-cohort design can be a useful tool for quickly estimating penetrance from volunteers in a setting in which the mutation prevale nce is relatively high.