Delgado-Cruzata Lissette, Zhang Wenfei, McDonald Jasmine A, Tsai Wei Yann, Valdovinos Cristina, Falci Laura, Wang Qiao, Crew Katherine D, Santella Regina M, Hershman Dawn L, Greenlee Heather
Departments of Environmental Health Sciences, Department of Sciences, John Jay College of Criminal Justice, City University of New York, New York, NY.
Biostatistics, and.
J Nutr. 2015 Apr;145(4):783-90. doi: 10.3945/jn.114.202853. Epub 2015 Feb 4.
Lower levels of global DNA methylation in tissue and blood have been associated with increased cancer risk. Conversely, cross-sectional analyses of healthier lifestyle patterns have been associated with higher levels of global DNA methylation.
In this trial, we explored the associations between changes in lifestyle modifications (diet, weight loss), metabolic markers, and global epigenetic biomarkers in white blood cells.
Study participants were Hispanic, African American, and Afro-Caribbean overweight and sedentary female breast cancer survivors (n = 24) who participated in a larger randomized, crossover, pilot study of a 6-mo weight loss intervention and who had available blood specimens. Anthropometric measures, a food-frequency questionnaire, and peripheral blood were collected at baseline, 6 mo, and 12 mo. Plasma samples were analyzed for metabolic markers (insulin, glucose). We measured DNA methylation of long interspersed nucleotide element 1 (LINE-1) and satellite 2 by pyrosequencing and MethyLight, respectively, and global DNA methylation by the luminometric methylation assay (LUMA).
DNA methylation of LINE-1 was statistically significantly elevated at 6 mo [75.5% vs. 78.5% (P < 0.0001)] and 12 mo [75.5% vs. 77.7% (P < 0.0001)], compared to baseline. Over a 12-mo period, changes in percentage body fat and plasma glucose concentrations were positively associated with LINE-1 DNA methylation (β = 0.19, P = 0.001) and LUMA DNA methylation levels (β = 0.24, P = 0.02), respectively. Similarly, 12-mo changes in dietary measures such as vegetable (β = 0.009, P = 0.048), protein (β = 0.04, P = 0.001), and total caloric (β = 0.05, P = 0.01) intake were positively associated with changes in LUMA DNA methylation, as was intake of fruit positively associated with changes in LINE-1 DNA methylation (β = 0.004, P = 0.02).
Our hypothesis-generating results suggest that lifestyle modifications may be associated with changes in global DNA methylation detectable at 6 and 12 mo. These biomarkers may be useful intermediate biomarkers to use in future intervention trials. This trial was registered at clinicaltrials.gov as NCT00811824.
组织和血液中整体DNA甲基化水平较低与癌症风险增加有关。相反，对更健康生活方式模式的横断面分析与更高水平的整体DNA甲基化有关。
在本试验中，我们探讨了生活方式改变（饮食、体重减轻）、代谢标志物与白细胞中整体表观遗传生物标志物之间的关联。
研究参与者为西班牙裔、非裔美国人和非裔加勒比超重且久坐不动的女性乳腺癌幸存者（n = 24），她们参与了一项为期6个月的减肥干预随机交叉试点研究，且有可用的血液样本。在基线、6个月和12个月时收集人体测量指标、食物频率问卷和外周血。分析血浆样本中的代谢标志物（胰岛素、葡萄糖）。我们分别通过焦磷酸测序和甲基化荧光定量PCR法测量长散在核元件1（LINE-1）和卫星2的DNA甲基化，并通过发光甲基化检测法（LUMA）测量整体DNA甲基化。
与基线相比，LINE-1的DNA甲基化在6个月时[75.5%对78.5%（P < 0.0001）]和12个月时[75.5%对77.7%（P < 0.0001）]有统计学显著升高。在12个月期间，体脂百分比变化和血浆葡萄糖浓度分别与LINE-1 DNA甲基化（β = 0.19，P = 0.001）和LUMA DNA甲基化水平（β = 0.24，P = 0.02）呈正相关。同样，蔬菜（β = 0.009，P = 0.048）、蛋白质（β = 0.04，P = 0.001）和总热量（β = 0.05，P = 0.01）摄入等饮食指标的12个月变化与LUMA DNA甲基化变化呈正相关，水果摄入与LINE-1 DNA甲基化变化呈正相关（β = 0.004，P = 0.02）。
我们产生假设的结果表明，生活方式改变可能与6个月和12个月时可检测到的整体DNA甲基化变化有关。这些生物标志物可能是未来干预试验中有用的中间生物标志物。本试验在clinicaltrials.gov上注册为NCT00811824。
