Familial and sporadic human renal cell carcinoma: evidence against a double-loss mechanism of carcinogenesis.
It has been speculated that renal cell carcinoma (RCC) is an example of 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 Israeli Jews] according to the multi-hit and clonal growth models of carcinogenesis. The analysis rules out a double-loss mechanism for RCC. On both of the two models analyzed, carcinogenesis in the familial cases of RCC arises as a result of a three- to ten-fold increase in the average rate of mutation at the susceptible loci, as compared with the sporadic cases. In general, the clonal growth model provides a somewhat better fit to the age-distribution of RCC incidence than does the multi-hit model.
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Department of Biochemistry, Silberman Institute of Life Sciences, Hebrew University, Jerusalem, Israel.
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D000328:Adult; D017677:Age Distribution; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D005260:Female; D006801:Humans; D015994:Incidence; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D009154:Mutation; D012042:Registries