Colorectal Cancer Incidence Linking Model in Familial Adenomatous Polyposis and the General Population

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A model was developed to account for the age distribution of colorectal cancer (CC) incidence among familial adenomatous polyposis (FAP) and in the general population. Estimated cumulative incidence rate of CC among 1050 FAP patients was 25% at age 33, 50% at age 41 and 75% at age 50. In the general population, estimated cumulative incidence rate of CC was 0.8% at age 60, 11.9% at age 70 and 3.7% at age 80. We modeled a hypothesis that a cancer cell starts clonal expansion when a certain number of independent rate-limiting mutations is accumulated, and the clone is clinically detected after a relatively long duration of progression. Using expression, 1-(1-(1-exp(-m.age))P)N for mutation accumulation and a lognormal progression duration with median 9 years for clinical detection, we could produce the age distribution for FAP patients, when m (mutation rate)=6/105 cells per year, p (number of mutations)-3 and N (number of stem cells)=108. The model fitted in the general population if p=4, with other parameters unchanged. Our results suggests that a number of rate-limiting processes in CC carcinogenesis is 3 for FAP and 4 for the general population and the difference is a single mutation. J Epidemiol, 1993; 3 : 109-115.
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