Catechol-O-methyltransferase, COMT, is an important phase II
enzyme catalyzing the transfer of a methyl-group from
S-adenosylmethionine to a
catechol-containing substrate molecule. A genetic variant Val158Met in the COMT gene leads to a several-fold decrease in the enzymatic activity giving rise to the accumulation of potentially carcinogenic endogenous
catechol estrogens and their reactive intermediates and increasing thus the risk of
tumorigenesis. However, numerous association studies between the COMT genotype and susceptibility to various
malignancies have shown inconsistent and controversial findings indicating that additional gene-gene and gene-environment interactions might be crucial in modulating the physiological role of the COMT. In this review article, the important contribution of dietary
catechol-containing
flavonoids to modification of the relationships between the COMT genotype and
cancer risk is discussed. Whereas, the diverse anticancer activities of common
phytochemicals, such as
green tea polyphenols,
quercetin,
fisetin or
luteolin, can be markedly changed (both decreased or increased) by the COMT-mediated O-methylation of these exogenous substrates,
flavonoids can also behave as potent inhibitors of the COMT
enzyme slowing detoxification of endogenous
catechol estrogens. Such a many-featured functioning of the COMT and its complex regulation by several different genetic and environmental factors, including plant-based
food ingredients, emphasizes the necessity to further stratify the association studies between the COMT genotype and
tumor risk by consumption of
catechol-containing dietary
flavonoids. Currently, it can be only speculated that some of the possible associations might be masked by the regular intake of specific food
polyphenols, taking effect in certain communities or populations.