THE COMT-MEDIATED METABOLISM OF FLAVONOIDS AND ESTROGEN AND ITS RELEVANCE TO CANCER RISK
 
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Pol. J. Food Nutr. Sci. 2003;53(Special issue 1s):141–146
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ABSTRACT
Catechol-O-methyltransferase (COMT) is the Phase II enzyme able to efficiently catalyze detoxification of endo- and exogenous compounds containing catechol groups which otherwise may become toxic, mutagenic or even carcinogenic. Therefore, the enzyme activity itself and the factors which influence the kinetics of such an inactivation are extensively studied. The COMT gene contains a single-nucleotide polymorphism (SNP), which is associated with an amino acid shift val -> met. This gene is present in up to 75% of Caucasians. Such a mutation results in a significant decrease in enzyme activity. It was shown in several studies that individuals having the low activity allele (COMTL) face greater risk for developing breast cancer. The development of carcinogenesis may originate from catechol metabolites of estrogen which are not sufficiently O-methylated into inactive compounds because of low COMT activity. Beside this genetic determinant, an expression of the enzyme in a given individual or in a population is likely to be affected by environmental and lifestyle factors. Particularly, exogenous compounds which compete for enzyme activity, like dietary polyphenol with catechol motif, the drug being a direct or indirect COMT inhibitor, or long-term exposure to exogenously administrated estrogen may contribute to carcinogenicity. COMT transfers a methyl group from S-adenyl-L-methionine to the catechol substrate. Therefore, the differences in metabolism of folate may also affect the individual response to catechol inactivation and then the cancer risk. Relationships between the level of endogenous DNA modifications involved in risk cancer and polymorphism in COMT gene, dietary habits, particularly high-flavonoid diet as well as life style (estrogen level and drugs) are discussed in the paper.
ISSN:1230-0322