Multistage models and primary prevention of cancer

Removal of carcinogenic exposures should reduce the subsequent risk for developing cancer. Of interest are the extent of the reduction and the speed with which it takes place. Multistage models with more than two stages for tumor development predict different patterns of chaniging risk following removal of a carcinogenic exposure, depending upon the stage in the process that the carcinogen predominantly affects. The fall in risk following removal of a early-stage carcinogen is only slowly evident, whereas removal of a late-stage carcinogen leads to a more rapid reduction in excess risk. Experimental and epidemiologic data are reviewed, and both early- and late-stage effects are seen. The long-term danger arising from entry into the environment of early-stage carcinogens is discussed, and it is shown that by the time human evidence that a hazard does exist becomes available, those already exposed may well have accumulated their fully effective doses.