Heterogeneity of cancer risk due to stochastic effects.

Persons with exactly the same genetic background, behavior, environment, etc. may have differences in cancer risk due to a different number of cells on the way to malignancy. These differences are estimated quantitatively by using the two-stage clonal expansion model. For liver cancer the estimated relative risk for persons without intermediate cells at age 40 is less than 10% when compared to the risk of the total population, while the top 0.1% risk group has a more than 100-fold risk compared to the population. The risk of the 1% percentile in risk is more than 100-fold of the risk of the more than 95% persons without intermediate cells. The number of intermediate (premalignant) cells in the risk groups cannot be calculated from incidence data only because they depend strongly on a nonidentifiable parameter. But under plausible assumptions, less than about 1,000 intermediate cells are present at age 40 even in high-risk persons.