Department of Nutrition Science; Friedman School of Nutrition Science and Policy; Tufts University; Boston, MA, USA.
Epigenetics. 2012 Jun 1;7(6):606-14. doi: 10.4161/epi.20236.
Altered levels of global DNA methylation and gene silencing through methylation of promoter regions can impact cancer risk, but little is known about their environmental determinants. We examined the association between lifestyle factors and levels of global genomic methylation and IL-6 promoter methylation in white blood cell DNA of 165 cancer-free subjects, 18-78 years old, enrolled in the COMIR (Commuting Mode and Inflammatory Response) study, New York, 2009-2010. Besides self-administrated questionnaires on diet and physical activity, we measured weight and height, white blood cell (WBC) counts, plasma levels of high sensitivity C-reactive protein (hs-CRP), and genomic (LINE-1) and gene-specific methylation (IL-6) by pyrosequencing in peripheral blood WBC. Mean levels of LINE-1 and IL-6 promoter methylation were 78.2% and 57.1%, respectively. In multivariate linear regression models adjusting for age, gender, race/ethnicity, body mass index, diet, physical activity, WBC counts and CRP, only dietary folate intake from fortified foods was positively associated with LINE-1 methylation. Levels of IL-6 promoter methylation were not significantly correlated with age, gender, race/ethnicity, body mass index, physical activity or diet, including overall dietary patterns and individual food groups and nutrients. There were no apparent associations between levels of methylation and inflammation markers such as WBC counts and hs-CRP. Overall, among several lifestyle factors examined in association with DNA methylation, only dietary folate intake from fortification was associated with LINE-1 methylation. The long-term consequence of folate fortification on DNA methylation needs to be further evaluated in longitudinal settings.
全球 DNA 甲基化水平的改变和启动子区域的基因沉默会影响癌症风险，但人们对其环境决定因素知之甚少。我们研究了生活方式因素与 165 名无癌症的研究对象白细胞 DNA 中全基因组甲基化和白细胞介素 6 启动子甲基化水平之间的关系，这些对象年龄在 18-78 岁之间，参与了 2009-2010 年纽约的 COMIR（通勤方式和炎症反应）研究。除了自我管理的饮食和身体活动问卷外，我们还通过外周血白细胞的焦磷酸测序测量了体重和身高、白细胞（WBC）计数、血浆超敏 C 反应蛋白（hs-CRP）水平以及基因组（LINE-1）和基因特异性甲基化（IL-6）。LINE-1 和 IL-6 启动子甲基化的平均水平分别为 78.2%和 57.1%。在调整年龄、性别、种族/民族、体重指数、饮食、身体活动、WBC 计数和 CRP 的多变量线性回归模型中，仅来自强化食品的膳食叶酸摄入与 LINE-1 甲基化呈正相关。IL-6 启动子甲基化水平与年龄、性别、种族/民族、体重指数、身体活动或饮食无关，包括总体饮食模式和个别食物组和营养素。甲基化水平与白细胞计数和 hs-CRP 等炎症标志物之间没有明显关联。总体而言，在所检查的与 DNA 甲基化相关的几种生活方式因素中，只有来自强化食品的膳食叶酸摄入与 LINE-1 甲基化有关。需要在纵向环境中进一步评估叶酸强化对 DNA 甲基化的长期影响。
