Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, China.
Epidemiology Research Unit, the First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Sci Rep. 2016 Jul 12;6:29555. doi: 10.1038/srep29555.
This study aimed to examine the joint effects of folate intake, polymorphisms of 5,10- methylenetetrahydrofolate reductase (MTHFR), methionine synthesis reductase (MTRR) and methionine synthase (MTR) genes and breast cancer risk. A case-control study of 570 consecutively recruited breast cancer cases and 576 controls was conducted in Guangzhou, China. Multifactor dimensionality reduction and logistic regression approach were used to evaluate gene-gene interaction. The covariates were chosen based on comparison of baseline characteristics of cases and controls. Folate intake was found to be inversely associated with breast cancer risk. The MTRRrs162036 GG genotype was associated with a decreased risk of breast cancer [adjusted odds ratio (OR) 0.41, 95% confidence interval (CI) 0.20-0.85]. Compared with the wild-type group (MTRRrs162036 AA with MTRrs1805087 AA) MTRRrs162036 AA with MTRrs1805087 GA + GG was associated with a decreased risk (OR 0.70, 95% CI 0.48-1.03). With the combined MTHFRrs1801131 TT and MTHFRrs1801133 GG genotypes as a reference, MTHFRrs1801131 TT with MTHFRrs1801133 GA + AA was associated with a decreased risk (OR 0.78, 95% CI 0.57 - 1.08) and MTHFRrs1801131 GT + GG with MTHFRrs1801133 GA + AA was associated with an increased risk (OR 1.35, 95% CI 0.88-2.05). The joint impact of MTRRrs162036 and MTRrs1805087, MTHFRrs1801131 and MTHFRrs1801133, folate and MTHFRrs1801133 may contribute to breast cancer risk.
本研究旨在探讨叶酸摄入量、5,10-亚甲基四氢叶酸还原酶（MTHFR）、蛋氨酸合成还原酶（MTRR）和蛋氨酸合成酶（MTR）基因多态性与乳腺癌风险的联合效应。在中国广州，进行了一项病例对照研究，共纳入 570 例连续招募的乳腺癌病例和 576 例对照。多因素维度缩减和逻辑回归方法用于评估基因-基因相互作用。根据病例和对照的基线特征比较选择协变量。叶酸摄入量与乳腺癌风险呈负相关。MTRRrs162036 GG 基因型与乳腺癌风险降低相关[调整后的比值比（OR）0.41，95%置信区间（CI）0.20-0.85]。与野生型组（MTRRrs162036 AA 与 MTRrs1805087 AA）相比，MTRRrs162036 AA 与 MTRrs1805087 GA+GG 与乳腺癌风险降低相关（OR 0.70，95%CI 0.48-1.03）。以 MTHFRrs1801131 TT 和 MTHFRrs1801133 GG 基因型的联合 MTHFRrs1801131 TT 与 MTHFRrs1801133 GA+AA 与乳腺癌风险降低相关（OR 0.78，95%CI 0.57-1.08）和 MTHFRrs1801131 GT+GG 与 MTHFRrs1801133 GA+AA 与乳腺癌风险增加相关（OR 1.35，95%CI 0.88-2.05）。MTRRrs162036 和 MTRrs1805087、MTHFRrs1801131 和 MTHFRrs1801133、叶酸和 MTHFRrs1801133 的联合作用可能导致乳腺癌风险。
