Detox Genes : The Pathway to Cancer

Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more water-soluble compounds. Xenobiotic biotransformation is accomplished by a limited number of enzymes with broad substrate specificities. Liver is considered to be the main center of detoxification. The result of biotransformation in most cases is detoxification; nevertheless, metabolism of some xenobiotics produces metabolites more reactive than their substrate compound and leads to harmful changes. The biotransformation system involves several enzyme systems that are commonly divided into two phases. Phase I enzymes are responsible for oxidation, reduction or hydrolysis and can be either detoxifying or activating. Phase II enzymes exert mainly detoxifying potential by conjugation. The cytochrome P450 enzyme superfamily, including CYP1A1 and CYP2E1 constitutes the majority of Phase I enzymes, while the microsomal epoxide hydrolase (mEH), N-acetyl transferases (NATs) and Glutathione S-Transferases are phase II enzymes primarily responsible for detoxification of xenobiotics. Accumulating data suggest that genetic polymorphisms in genes controlling carcinogen metabolism is responsible for the individual variations in cancer risk. From the broad literature available, the current book project summarizes the role specific polymorphisms in genes encoding xenobiotic metabolism, in predisposing the individuals to various cancers.