Estrogen-DNA adduct ratios as a predictor for breast cancer risk in premenopausal Asian women

Abstract Background The incidence of breast cancer among East Asian women has been increasing rapidly in recent decades, but the etiology remains unclear. This case–control study investigated whether estrogen-DNA adducts ratio is a predictor of breast cancer risk in East Asian women. Methods The control group (n = 146) comprised healthy female volunteers and women with benign breast disease without atypia. The case group (n = 221) comprised women either with benign breast disease with atypia and breast cancer. The ratios of estrogen-DNA adducts to their respective metabolites and conjugates in plasma were analyzed using ultraperformance liquid chromatography and tandem mass spectrometry. The single nucleotide polymorphisms (SNPs) of CYP1A1, CYP1B1, and COMT were genotyped, and a logistic regression model was used to compare the estrogen-DNA adduct ratios between the two groups. Results 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, P = 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, P < 0.001). However, the CYP1A1, CYP1B1, and COMT SNPs were not associated with the estrogen-DNA adduct ratios. Conclusion Plasma estrogen-DNA adduct ratio predicts breast cancer risk in premenopausal women in East Asia, and the genotoxic effects may contribute to the carcinogenesis of this emerging disease.