Gene Environment Interactions

Another way in which inherited susceptibility to cancer may be expressed is the way in which an individual can handle carcinogenic insults from the environment. For example, some individuals have a reduced capacity to metabolize carcinogens such as arylamines because of a slow acetylator phenotype, related to polymorphisms in the N-acetyltransferase-2 gene. Others may have a decreased ability to detoxify a number of carcinogenic agents due to polymorphisms in the glutathione S-transferase gene GSTM-1 or cytochrome P-450 genes CYP2A6 or CYP2D6. Genes that regulate metabolism of drugs and other xenobiotics are often discussed under the heading of pharmacogenetics. A number of genetic polymorphisms that are related to human pharmacogenetic disorders are listed in Table 3—11. Evidence from a study of monozyotic

Table 3—11. Classification of Some Human Pharmacogenetic Disorders

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