Genetics and the etiology of childhood cancer.

A consideration of the world-wide incidences of childhood cancer and of hereditary subgroups leads to the conclusion that two successive mutations can initiate cancer cells and that such cells usually proceed to develop into detectable cancers in a period of time which is short compared with the time required for most adult cancers. Environmental carcinogens could hypothetically increase the rates at which these mutations occur, but they probably, in fact, contribute little to the incidences. Certain exceptions, notably leukemia and lymphoma, are noteworthy, and a viral origin for them has been widely hypothesized. If most solid tumors of childhood are indeed correctly attributable to mutations in germ and/or somatic cells, then the prospect for the prevention of childhood cancer becomes very dim. In fact, the incidence of the germinal forms may increase as treatment improves (18). In theory, one might be able to identify individuals harboring cancer genes germinally and even to identify them prenatally. But even if the burden of cancer attributable to the hereditary subgroups were elimanted, there would still remain the larger nonhereditary group resulting from somatic mutations. If this hypothesis is correct, then childhood cancer cannot be prevented. With this conclusion goes the admonition, however, that environmental mutagens might significantly increase the burden of childhood cancer. One such mutagen, therapeutic radiation, is known to increase the prospect that second tumors will occur in patients who carry a germinal cancer mutation. The major effort to reduce the incidence of childhood cancer by prevention should be spent in examining the possibility that leukemia and lymphoma are viral in origin. If the arguments presented are correct, then the main effort against childhood cancer must be that of early diagnosis and treatment. I realize that many have already argued for that strategy in the approach to cancer generally, but I now believe that it is particularly relevant to any program against cancer in children.