Sulfotransferase 1A1 as a Biomarker for Susceptibility to Carcinogenesis: From Molecular Genetics to the Role of Dietary Flavonoids.

BACKGROUND: Sulfotransferase (SULT) 1A1 is a phase II metabolic enzyme that catalyzes sulfate conjugation of various phenolic compounds, including endogenous substances, such as estrogens and thyroid hormones, but also different xenobiotics. Although sulfation is classically considered as a detoxification event facilitating the excretion of more water soluble metabolites from the body, in some cases such bioconversion may also lead to bioactivation of promutagens, producing highly reactive intermediates which are capable of damaging DNA and promoting carcinogenesis. The most common polymorphism in SULT1A1 (Arg213His) has an important functional impact by affecting the capacity to sulfate diverse substrates and numerous case-control studies have shown associations between SULT1A1 variants and susceptibility to different malignancies. Several factors may significantly influence such relationships, including ethnicity, gender, parity, menopausal status, use of estrogen replacement therapy, exposure to tobacco smoke or occupational chemicals. RESULTS AND
CONCLUSION: In this review article, we show that one more important determinant should be considered as a stratifying factor in studies of possible associations between SULT1A1 variants and cancer risk, i.e., the dietary intake of different flavonoids. As sulfation of bioactive plant polyphenols can change their potential anticancer activities and, on the other hand, these phytochemicals are capable to behave also as potent SULT1A1 inhibitors, the regular dietary exposure of humans to these compounds can make a great contribution to the impact of sulfation capacity on individual susceptibility to carcinogenesis. The effect of specific flavonoids as well as their interactions with other factors on associations between SULT1A1 alleles and cancer risk certainly needs further thorough studies.