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

• Published in: Cancer prevention research (Philadelphia, Pa.) Pa.), 2023-03, Vol.16 (3), p.153-161
• Main Authors: Lin, Ching-Hung, Zahid, Muhammad, Kuo, Wen-Hung, Hu, Fu-Chang, Wang, Ming-Yang, Chen, I-Chun, Beseler, Cheryl L, Mondal, Bodhisattwa, Lu, Yen-Shen, Rogan, Eleanor G, Cheng, Ann-Lii
• Format: Article
• Language: English
• Subjects: Breast Neoplasms - etiology; Breast Neoplasms - genetics; Case-Control Studies; Cytochrome P-450 CYP1A1; DNA Adducts; Estrogens - metabolism; Female; Humans
• ISSN: 1940-6207; 1940-6215
• DOI: 10.1158/1940-6207.CAPR-22-0415

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 (n = 146) comprised healthy female volunteers and women with non-proliferative breast disease. The case group (n = 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 CYP1A1, CYP1B1, and COMT 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, 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. 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. 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.