FAMILIAL AND SPORADIC HUMAN RENAL-CELL CARCINOMA - EVIDENCE AGAINST ADOUBLE-LOSS MECHANISM OF CARCINOGENESIS

It has been speculated that renal cell carcinoma (RCC) is an example o f a double-loss mutation. We analyzed the age distribution of 71 cases of familial RCC and of 11 population-based cancer registries [German Democratic Republic, Denmark, Finland, Norway, Sweden, U.S.A. Whites, U.S.A. Blacks, Miyagi and Osaka Prefectures (Japan), Hong Kong, and Is raeli Jews] according to the multi-hit and clonal growth models of car cinogenesis. The analysis rules out a double-loss mechanism for RCC. O n both of the two models analyzed, carcinogenesis in the familial case s of RCC arises as a result of a three- to ten-ford increase in the av erage rate of mutation at the susceptible loci, as compared with the s poradic cases. In general, the clonal growth model provides a somewhat better fit to the age-distribution of RCC incidence than does the mul ti-hit model.