ReviewArticle GeneticPolymorphismof Enzymes Involved in Xenobiotic the Risk ofLung Cancer Metabolismand

Chronic inhalation of cigarette smoke is a major risk factor for the development of lung cancen It has been sllggested that genetic susceptibility may contribute to the risK because only a small portion of smokers develops the disease. Seyeral polymorphisms that involve the metabolic activation or detoxification of carcinogens deriyed from cigarette smoke have been found to be associated with lung cancer risk. Many studies haye focused on the relation between the distribution ef polymerphic variants of different forms of the metabolic enzymes and lung cancer susceptibility In this respect two groups of genetic polymorphisms of enzymes involved in xenobiotic metabolism, cytochrome P450 (C}CP) and glutathione S-transferases ((ZSts), haye been discussed. C}CP multigene superfamily consists of 10 subfamMes (C}CPI-Cyple). A positiye asseciation between deyelopment of lung cancer and the mutant homozygous genotype of CZPiAl gene has been reported in several Japanese populations but such an association has not been observed in either Caucasians or African-Americans. The relation between CTI?2D6 and lung cancer remains conflicting alld inconclusiye. Seyeral polymorphisms haye been identified at the CVR2El locus. No definitive link between the polymorphisms of C}[P2El and the risk of lung caneer has, howeye4 been identified. The role of other CZP2 isoforms in lung carcinogenesis has not been sufflciently investigated. (ZSfs form a superfamily of genes consisting of fiye distinct families, named (IS7]4, asTlld; (IS7111 (lgTT and (IS71S. The role of (ZSTM, (ISTTI or (iST:Pl polymorphism in modifying the lung cancer risk may be more limited than has been so far