[Genetic and phenotypic polymorphisms in carcinogen-metabolizing enzymes and cancer susceptibility]

Most of chemical carcinogens require metabolic activation before they interact with cellular macromolecules and can cause cancer initiation. Many of cytochrome P-450 (CYP) mediating oxidative enzymes and conjugation enzymes, cloned and characterized in humans, show genetic and phenotypic polymorphisms and have been suggested to contribute to individual cancer susceptibility as genetic modifiers of cancer risk. Altered phenotypes and genotypes in CYP1A1, CYP2D6 and CYP2E1 and in defective glutathione S-transferase (GST) and N-acetyltransferase enzymes have been associated with an increased risk of developing lung and other cancers. The risk to lung cancer is dramatically increased in the population carried simultaneously high-risk genotypes in CYP1A1 and GSTM1. There are, however, several studies in each category in which no association have been found.