18 - Genetic and other host-risk factors

Summary

Introduction

Cancer results ultimately from an interplay between genetic and environmental factors. Since the genetic background, lifestyle, and the external and internal environment of human populations are highly variable, three categories of cancers caused by different genetic environmental interactions can be delineated.

Heritable cancers which are largely independent of the environment and where genetic variation appears to be the major determinant are characterized by familial aggregation, and usually occur earlier than non-heritable tumors. They may be associated with other phenotypic manifestations such as a characteristic clinical syndrome preceding their appearance. Probably only a minor fraction, 1–2%, of all cancers are of this type.

Cancers produced by environmental agents in genetically predisposed individuals include syndromes involving an elevated risk of a specific cancer when appropriate environmental conditions occur. Some syndromes derive from the presence in the homozygous state of single autosomal recessive genes. However, only for individuals with xeroderma pigmentosum is the specific environmental agent known, notably exposure to ultraviolet light.

Cancers largely induced by environmental agents, for example, lung cancer due to tobacco smoking, bladder cancer due to aromatic amine exposure, were hitherto considered independent of genetic variation. As is true for the majority of malignant neoplasms. Recent studies suggest, however, that several such cancers are modified by inherited host factors and thus also have a genetic component.