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Genetic Factors in the Etiology of Cancer

Laboratory of Biology, National Cancer Institute, USPHS, Bethesda, Maryland

Genetic factors in the etiology of cancer are discussed as they are of concern to the epidemiologist. Results of basic studies in experimental animals do not foretell simple inheritance of cancer in man. Most types of cancer are inherited as threshold characters in which the cancer results from the interplay of multiple genetic and nongenetic factors. Response to carcinogens is controlled by the genotype of the individual, and thus the problem with environmental carcinogens will pertain for the most part to the genetically susceptible individuals. The propagation and transmission of tumor viruses are influenced by the genotype of the host, one of the more simple relationships being with the Rous sarcoma virus that appears to be controlled by a single dominant gene. This points to certain obstacles in the identification and study of possible human tumor viruses. Many specific genes on many chromosomes in the mouse have been shown to increase or decrease the occurrence of specific types of tumors. Often the genetic effect can be localized as controlling the response of the end organ, but other gene action paths have been demonstrated. Identification of the action of these genes at the biochemical level can be expected soon with the rapid development of biochemical genetics in the mouse and in mammalian cells. More knowledge of the malignant change can be expected from well-controlled studies in tissue culture. The possibility that this change may be related to readily observed gross chromosomal changes is discussed, but it is concluded that the basic malignant transformation is more likely to be some change in structure or function at the level of the gene.