外周血全基因组DNA甲基化在甲基供体与乳腺癌关系中作用的研究  

Effect of peripheral bloodgenomic DNA methylation on the relationship between methyl donor status and risk of breast cancer

作　　者：罗伟平[1,2] 杜雨峰[1] 黄靖[1] 黄武卿 徐铭[1] 严波[1] 莫雄飞[3] 张彩霞[1] 

机构地区：[1]中山大学公共卫生学院医学统计与流行病学系,广州510080 [2]广州医科大学附属广州市第一人民医院预防保健科,510180 [3]中山大学附属第一医院血管甲状腺外科,广州510080

出　　处：《中华流行病学杂志》2017年第4期537-541,共5页Chinese Journal of Epidemiology

基　　金：国家自然科学基金（81102188）;广州市科技计划项目科学研究专项（201510010151）

摘　　要：目的 探讨外周血全基因组DNA甲基化在甲基供体（叶酸、蛋氨酸、总胆碱、甜菜碱）与乳腺癌发病关系中的作用。方法 采用病例对照研究设计，共纳入300例乳腺癌病例和300例对照。采用食物频数问卷调查研究对象的膳食摄入并计算甲基供体的摄入量。采集研究对象外周血提取DNA，使用MethylFlashTM Methylated DNA Quantification Kit（Colorimetric）进行全基因组DNA甲基化分析。运用路径分析表现甲基供体摄入、全基因组DNA甲基化程度和乳腺癌发病之间的相互关系。结果 病例组和对照组外周血全基因组DNA甲基化率分别为0.46% ± 0.25%和0.53%±0.34%，病例组低于对照组，差异有统计学意义（P〈 0.01）。路径分析结果显示，蛋氨酸摄入与外周血全基因组DNA甲基化程度呈正相关（β=0.065，P〈 0.05），而外周血全基因组DNA甲基化程度与乳腺癌发病风险呈负相关（β=-0.027，P〈 0.05）。结论 乳腺癌病例外周血全基因组DNA甲基化程度低于对照组人群。外周血全基因组DNA甲基化在蛋氨酸摄入与乳腺癌发病风险之间起了中介作用。Objective To explore the effect of peripheral blood genomic DNA methylation on the relationship between methyl donor status and risk of breast cancer. Methods A case-control study was conducted. Each three hundred breast cancer cases and controls were consecutively recruited. Food frequency questionnaire was used to collect dietary information. Amounts on folate, methionine,choline and betaine intake were calculated. Blood samples were collected for DNA extraction. Peripheral blood genomic DNA methylation was measured by using the Methyl FlashTM Methylated DNA Quantification Kit. Pathway analysis was used to examine the effect of genomic DNA methylation on the relations between methyl donor status and risk of breast cancer. Results The genome DNA methylation rates were 0.46%±0.25% and 0.53%±0.34%, respectively on both cases and controls, with differences statistically significant （P〈 0.01）. Results from the pathway analysis, results showed that methionine consumption was related to genomic DNA methylation （β=0.065, P〈 0.05） while genomic DNA methylation was related to the risk of breast cancerk （β=-0.027, P〈 0.05）,respectively. Conclusions The level of peripheral blood genomic DNA methylation in breast cancer cases was significantly lower than that in the controls. Genomic DNA methylation seemed to have played a mediated role between methionine and the risk of breast cancer.

关 键 词：乳腺癌 DNA甲基化 甲基供体 

分 类 号：R737.9[医药卫生—肿瘤]