Glucuronidation of Catechol Estrogens by Expressed Human UDP-Glucuronosyltransferases (UGTs) 1A1, 1A3, and 2B7,

Genetic polymorphisms in the UDP-glucuronosyltransferase 1A1 (UGT1A1) gene and prostate cancer risk in Caucasian men

“…The rationale of the present study was that alteration in the glucuronidation pathway, which directly inactivates estrogens and catechol metabolites at their site of action, may potentially modify estrogen concentration and consequently estrogen-related cancer risk. In support of this scenario, functional studies on the transcriptional promoter activity have already demonstrated that the TA(7)/TA(7) genotype causes a 30% decrease in transcription leading to an altered enzyme expression and therefore, low enzymatic activity [7,8]. In addition, several studies based on phenotypic measurements revealed that those who were carriers of at least one (TA)7 allele had much lower glucuronidation rates compared with homozygous (TA)6 [9,10].…”

“…Among UGTs, UGT1A1 has been shown to catalyze the glucuronidation of catechol estrogens, leading to their enhanced elimination via urine or bile [8]. It is expressed extensively in the liver and to a lesser extent in other organs, including prostate [6].…”

The association between TA-repeat polymorphism in the promoter region of UGT1A1 and breast cancer risk: a meta-analysis

“…The control groups may have different risks of developing breast cancer. Fourth, data were not stratified by menopausal status (UGT1A1 plays an important role in metabolism of estrogens [2,3,17]), age, smoking status, and other factors. Therefore, a more precise analysis should be conducted if enough data were available.…”

“…Breast cancer is still a major challenge for women's health. Uridine diphospho-glucuronosyltransferase 1A1 (UGT1A1) encodes the enzyme which takes part in glucuronidation pathway in metabolism of estrogens [2,3], carcinogens [4,5], and drugs [6,7]. The estrogens and carcinogens were the main risk factors for breast cancer development [8,9].…”

2,3,7,8-Tetrachlorodibenzo-p-dioxin modulates estradiol-induced aldehydic DNA lesions in human breast cancer cells through alteration of CYP1A1 and CYP1B1 expression

“…Additionally, a high incidence of uterine adenocarcinoma was detected in female CD-1 mice after neonatal exposure to 4-OHE 2 or 2-OHE 2 [17]. Estrogen catechols are inactivated by several detoxification pathways, including O-methylation catalyzed by catechol-O-methyltransferase (COMT) [18][19][20][21]. Catechol estrogens form several DNA adducts via their quinone and semiquinone forms [22][23][24][25].…”