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.
Heidenreich
Wolfgang F
WF
GSF, Institute of Radiation Protection, Germany. heidenreich@gsf.de
D000328:Adult; D000368:Aged; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000473:pathology; D008297:Male; D008433:Mathematics; D008875:Middle Aged; D008954:Models, Biological; D009369:Neoplasms / Q000209:etiology* / Q000473:pathology; D016016:Proportional Hazards Models; D012307:Risk Factors; D013269:Stochastic Processes