Genetics, etiology, and human cancer

Abstract

Approximately 9% of the 2000 or more Mendelian inherited diseases of man have a cancer association. In the aggregate, these hereditary disorders account for perhaps 5–10% of all human cancer. However, myriad exogenous and endogenous factors influence the induction and promotion of both single gene and polygenically determined varieties of cancer. Cancer liability can be comprehended as a combination of genetic susceptibility and environmental exposure wherein the question becomes “What proportion of the variance in liability in a population can be attributed to the genetic component (heritability)?” It therefore is misleading to regard individual cases as being due to genetic or environmental factors, since these effects interplay in all patients. Typical clinical features of hereditary/familial cancer are early onset and multiple primary cancer. Predictability in such a setting relevant to specific target organs is of as high or higher an order of magnitude as the predictability of cancer in, for example, atomic bomb survivors, vinyl chloride and asbestos workers, or heavy cigarette smokers. This information can be utilized to great advantage through registries with management programs focusing on surveillance and prevention through avoidance of specific carcinogens, and in certain circumstances, prophylactic removal of high risk organs.