Data from Estrogen-DNA Adducts and Breast Cancer Risk in Premenopausal Asian Women

Abstract

<div>Abstract<p>The incidence of breast cancer among premenopausal women has been increasing rapidly in recent decades in East Asia. This case–control study investigated whether estrogen-DNA adducts were associated with breast cancer risk in Taiwan. The control group (<i>n</i> = 146) comprised healthy female volunteers and women with non-proliferative breast disease. The case group (<i>n</i> = 221) comprised women either with proliferative benign breast disease or breast cancer. The ratios of estrogen-DNA adducts to their respective metabolites and conjugates in plasma were analyzed using ultraperformance LC/MS-MS. The SNPs of <i>CYP1A1</i>, <i>CYP1B1</i>, and <i>COMT</i> were genotyped. Logistic regression model was used to compare the estrogen-DNA adduct ratios between the two groups. The estrogen-DNA adduct ratio in the case group was significantly higher than that in the control group (median ratio: 58.52 vs. 29.36, <i>P</i> = 0.004). A multiple logistic regression model demonstrated that a unit increase in the natural log of the estrogen-DNA adduct ratio in premenopausal women was a significant predictor of breast cancer risk, with an estimated hazard ratio of 1.718 (1.444−2.046, <i>P</i> < 0.001). However, the <i>CYP1A1</i>, <i>CYP1B1</i>, and <i>COMT</i> SNPs were not associated with the estrogen-DNA adduct ratios. In conclusion, plasma estrogen-DNA adduct ratio was associated with the presence of breast cancer or proliferating benign breast disease in premenopausal women in Taiwan.</p>Prevention Relevance:<p>This study provides evidence that endogenous estrogen-induced genotoxicity may contribute to the carcinogenesis of breast cancer in premenopausal Asian women. This work could have important preventive implication for the emerging disease in East Asia.</p></div>