Population aspects of cancer genetics.

A number of relatively rare, high-risk genes have been identified which predispose to common cancers such as breast, colon, and melanoma. Although these are clearly important in the clinical setting, it is also relevant to discuss the impact of these genes at the population level and to contrast these with that which could be ascribed to more common genetic variants which only confer a modest increased risk of cancer. In this review, we examine inferences about the role of genetics in cancer from ecological studies of incidence patterns from a number of population-based studies of familial and attributable risk. The relationship between the genetic model (genotypic risk, allele frequency, mode of inheritance) and the expected impact in the population in terms of both attributable risk and familial risk is presented. The advantages and limitations of using cancer occurrence in twins to measure the genetic contribution to specific cancer sites is discussed. The potential role of lower-penetrance genes in the overall cancer burden may be significant but may pose significant problems in the public health arena.