目标:在东亚,乳腺癌的发病率一直在快速增长,尤其是绝经前妇女。雌激素-DNA加合物的比例升高与乳腺癌的风险更高有关。本研究探讨了碱基切除修复(BER)基因多态性与雌激素-DNA加合物之间的相互作用对乳腺癌风险的影响。
方法:我们进行了一项病例对照研究,包括健康志愿者和良性乳腺疾病患者(对照组,n=176)和浸润性癌或原位癌患者(病例臂,n=177)。BER相关基因的基因分型,包括SMUG1,OGG1,ERCC5和APEX1。逻辑回归模型,整合基因多态性之间的相互作用,雌激素-DNA加合物比,和临床变量,用于确定乳腺癌的危险因素。
结果:单变量分析显示乳腺癌风险与APEX1rs1130409T>G(P=0.057)和APEX1rs1760944T>G(P=0.065)之间存在边缘关联。多变量回归分析显示,APEX1_rs1130409(GT/GG与TT)与雌激素-DNA加合物比的自然对数值(估计OR1.164,P=0.023)和绝经前状态与雌激素-DNA加合物比>2.93(估计OR2.433,P=0.001)的乳腺癌风险增加显着相关。
结论:APEX1_rs1130409(GT/GG与TT)多态性,这与BER活动减少有关,加上雌激素-DNA加合物的比例增加,增加东亚女性患乳腺癌的风险。
OBJECTIVE: In East Asia, the incidence of breast cancer has been increasing rapidly, particularly among premenopausal women. An elevated ratio of estrogen-DNA adducts was linked to a higher risk of breast cancer. The present study explored the influence of the interaction between base excision repair (BER) gene polymorphisms and estrogen-DNA adducts on breast cancer risk.
METHODS: We conducted a case-control study comprising healthy volunteers and individuals with benign breast disease (control arm, n = 176) and patients with invasive carcinoma or carcinoma in situ (case arm, n = 177). Genotyping for BER-related genes, including SMUG1, OGG1, ERCC5, and APEX1, was performed. A logistic regression model, incorporating interactions between gene polymorphisms, estrogen-DNA adduct ratio, and clinical variables, was used to identify the risk factors for breast cancer.
RESULTS: Univariate analysis indicated marginal associations between breast cancer risk and APEX1 rs1130409 T > G (P = 0.057) and APEX1 rs1760944 T > G (P = 0.065). Multivariate regression analysis revealed significant associations with increased breast cancer risk for APEX1_rs1130409 (GT/GG versus TT) combined with a natural logarithmic value of the estrogen-DNA adduct ratio (estimated OR 1.164, P = 0.023) and premenopausal status with an estrogen-DNA adduct ratio > 2.93 (estimated OR 2.433, P = 0.001).
CONCLUSIONS: APEX1_rs1130409 (GT/GG versus TT) polymorphisms, which are related to decreased BER activity, combined with an increased ratio of estrogen-DNA adducts, increase the risk of breast cancer in East Asian women.