Hereditary cancer, oncogenes, and antioncogenes

The somatic mutational hypothesis for the origin of cancer carries several implications of importance: (a) spontaneous mutations should produce some irreducible "background" level of cancer; (b) agents that can change the host genome by mutagenesis or by addition or deletion of genetic material should increase this background incidence: (c) abnormalities that favor either spontaneous or induced mutations should impose an elevated risk of cancer; and (d) inheritance of an initiating mutation should strongly predipose to cancer. These groups may be designated as "oncodemes," because they are demographic units with different expectations of cancer, depending upon environmental and hereditary variables. The somatic mutations hypothesis also implies that there are critical genetic loci with mutations that lead to cancer. Any attempt to understand the process of carcinogenesis would necessarily be concerned with discovering these genes and understanding their behavior in health and disease. The author now seems to have identified 2 large classes of such genes. The first class, consisting of the oncogenes, was originally discovered through the study of critical genes in the acutely transforming retroviruses. The second class includes "antioncogenes" and was identified through the study of the hereditary cancers of the fourth oncodeme.