Unbalanced estrogen metabolism in ovarian cancer

Abstract

Greater exposure to estrogens is a risk factor for ovarian cancer. To investigate the role of estrogens in ovarian cancer, a spot urine sample and a saliva sample were obtained from 33 women with ovarian cancer and 34 age-matched controls. Thirty-eight estrogen metabolites, conjugates and DNA adducts were analyzed in the urine samples by using ultraperformance liquid chromatography/tandem mass spectrometry, and the ratio of adducts to metabolites and conjugates was calculated for each sample. The ratio of depurinating estrogen-DNA adducts to estrogen metabolites and conjugates was significantly higher in cases compared to controls (p<0.0001), demonstrating high specificity and sensitivity. DNA was purified from the saliva samples and analyzed for genetic polymorphisms in the genes for two estrogen-metabolizing enzymes. Women with two low-activity alleles of catechol-O-methyltransferase plus one or two high-activity alleles of cytochrome P450 1B1 had higher levels of estrogen-DNA adducts and were more likely to have ovarian cancer. These findings indicate that estrogen metabolism is unbalanced in ovarian cancer and suggest that formation of estrogen-DNA adducts plays a critical role in the initiation of ovarian cancer.

Dietary fat intake and ovarian cancer risk: a meta-analysis of epidemiological studies

“…A reanalysis [49] of epidemiological data suggested estrogen monotherapy or estrogen and progesterone combination therapy could elevate the risk of ovarian cancer, specifically serous or endometroid tumors. In ovarian tissues, estrogen receptors are also expressed [66]; the ratios of estrogen-DNA adduct depurination to estrogen metabolites and conjugates in ovarian cancer cases are significantly higher than controls [67]. We speculated that hormonal pathways might play a positive role in the development of ovarian cancer.…”

Impact of estrogen and progesterone receptor expression on the clinical and molecular features of papillary thyroid cancer

“…An increased risk of thyroid cancer has also been documented in women who have been treated with estrogen for gynecological reasons and in women who were taking oral contraceptive pills (15). Interestingly, estrogen metabolites and conjugates have been found to be significantly higher in women with well-differentiated thyroid cancer as compared to age-matched control women (16).…”

The molecular etiology and prevention of estrogen-initiated cancers

“…After partial purification by solid phase extraction, an aliquot of each urine sample was analyzed for 38 estrogen metabolites, conjugates and depurinating DNA adducts by using UPLC-MS/MS, and the ratio of DNA adducts to metabolites and conjugates was calculated (Fig. 29) (Zahid et al, 2013a). Almost all of the women diagnosed with ovarian cancer had higher DNA adduct ratios (M=91.4 ± 43.1) than the healthy control women (M=24.7 ± 12.7), and the difference was highly significant (p < 0.0001).…”