Susceptibility to carcinogenesis

Abstract

This report examines qualitative and quantitative evidence that the spontaneous incidence of a specific type of tumor is one of the many factors which determine the incidence of carcinogen-induced tumors of the same type. To avoid selection bias in the choice of data for analysis, all suitable data used in a previous review on a closely related subject are analyzed. One method of attack consists of the mathematical elimination of factors other than spontaneous incidence which influence carcinogenesis. When unselected carcinogenesis data are examined without such elimination, then the spontaneous incidence often has no apparent effect on induced incidence. The explanation appears to be that the spontaneous incidence is a weak factor which has incomplete penetrance, and frequently is outweighed by other factors. Although the evidence examined is consistent with this conclusion, this does not constitute proof. Regarding mechanism, a carcinogen is seen to enhance the potential for the conversion of normal progenitor cells into cancer cells, which underlies the spontaneous incidence of tumors. It follows that carcinogen assays should be most sensitive, when the type of tumor induced by the carcinogen has a spontaneous incidence which is overt but low, or is just barely subthreshold.