Genetic etiology of cancer

Cancer may be considered a genetic disease at the cellular level, in that evidence from studies of chemical, radiation, and viral carcinogenesis, as well as cytogenetics and hereditary cancers, suggests that irreversible changes in the cellular hereditary material occur in the development of a cancer cell. Hereditary or environmental factors may influence that probability of such changes. A small fraction of human cancers may be attributed to rare hereditary disorders of chromosomal abnormality, mutagenesis, cell growth regulation or differentiation, or immune deficiency. Yet studies of familial cancer suggest that in the absence of such demonstrable abnormalities, a predisposition to cancer may follow an autosomal dominant hereditary pattern, generating tumors that occur at relatively early ages and which may be multiple. The occurrence of hereditary and nonhereditary forms of the same histologic cancer has been attributed to the occurrence of similar genetic changes in germinal or somatic cells, respectively. The percentage of tumors arising from germinal mutations varies for each tumor type, but may account for nearly 40% of certain childhood cancers, and a lesser percentage of adult cancers. Study of the interaction of hereditary and acquired risk factors suggests that more than a single genetic change may be necessary for cancer to develop. If a series of mutations are necessary, then those individuals with the inherited mutation present in all cells may be uniquely susceptible to carcinogens. Individuals genetically predisposed to cancer may be identified through family studies, recognition of associated anomalies or followup of patients with a previous cancer. Appropriate clinical examinations may lead to early cancer detection, and research studies may reveal genetic markers or early cellular changes predisposing to cancer. Cancer 40:438–444, 1977.