Genetic Carrier Frequency for Lung Cancer

Abstract

IN a review of the evidence relating to familial aggregations of malignant disease in man it was concluded¹ that these can generally be attributed to genetic factors. A similar conclusion² has since been drawn with respect to lung cancer in man. The commonest form of predisposing inheritance appears to be a simple Mendelian dominant of incomplete penetrance, although very occasionally (but especially with parental consanguinity) apparent recessive inheritance is observed in childhood leukæmia and lymphosarcoma¹. Although for a specific cancer the inherited predisposition usually affects only a single autosomal locus (perhaps one of several), the phenotypic expression in adults should generally involve somatic mutation of the gene homologous with the inherited allele, together with somatic mutation of homologous genes at another locus^1,3. From twins studies⁴, the typical penetrance of a predisposing allele in the phenotypic form of any malignancy is calculated to be about 0.3 (ref. 1), but for a life-span of 70 years it is likely to be slightly higher than this. Cancers arising in a genetic carrier are described as ‘prezygotic’; but where there is no specific predisposition, and where all mutational events are confined to somatic cells, the resulting cancer is described as ‘postzygotic’⁵. It was concluded that in the absence of powerful extrinsic carcinogens, most human malignancies are probably prezygotic¹. Extrinsic carcinogens should tend to change the balance in favour of postzygotic malignancies.