Multistage carcinogenesis and the incidence of human cancer.
We consider the implications of multistage carcinogenesis for the incidence of cancer in human populations. When clonal expansion of partially altered cells is properly accounted for, we find it unnecessary to invoke genomic instability as an early event in malignant transformation. Environmental agents that increase the rate of clonal expansion of partially altered cells are efficient carcinogens. As a corollary, intervention strategies that decrease this rate are to be preferred to strategies that decrease the rate of early mutational events in carcinogenesis.
Moolgavkar
Suresh H
SH
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. smoolgav@fhcrc.org
Luebeck
E Georg
EG
D000367:Age Factors; D004781:Environmental Exposure / Q000009:adverse effects; D006801:Humans; D015994:Incidence; D009367:Neoplasm Staging; D009369:Neoplasms / Q000139:chemically induced / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology