Genetic Determinants in Carcinogenesis
There are three types of risk factors that determine whether an individual will develop cancer — environmental exposures, intrinsic susceptibility, and age/time. It is important, therefore, to understand the genetic determinants underlying these risk factors. The critical target genes for environmental factors are, in part, known and include protooncogenes and tumor suppressor genes (Boyd and Barrett 1990; Bishop 1991). These are discussed further by Balmain, Bowden, and others in this volume. The genetic determinants for intrinsic susceptibility to cancer are of two types. On the one hand, genetic variations exist in genes that influence the impact of environmental agents on an individual, such as genes that control carcinogen metabolism or repair of carcinogenic damage (Hanawalt and Sarasin 1986; Lehmann and Dean 1990). On the other hand, individuals may inherit germ line mutations in genes that are directly involved in the neoplastic conversion of normal cells (Malkin et al. 1990). For example, inherited mutations in tumor suppressor genes can increase the risk of specific cancers. The magnitude of this increased risk can vary greatly depending on the number of additional steps required for the genesis of the tumor. For example, mutations in the rb gene increase the relative risk for retinoblastoma by 105-fold whereas the same mutation, increases the risk for lung cancer by only 10-fold (A. Knudson, personal communication).
KeywordsCellular Senescence Population Doubling Senescent Cell Werner Syndrome Population Doubling Level
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