Department of Epidemiology, Columbia University Medical Center, New York, NY, USA.
Cancer Epidemiol Biomarkers Prev. 2011 Dec;20(12):2518-23. doi: 10.1158/1055-9965.EPI-11-0553. Epub 2011 Oct 12.
Exposure to prenatal tobacco smoke (PTS) has been associated with a number of health outcomes in the offspring, including some childhood cancers. Lower levels of genomic DNA methylation have also been associated with several types of cancers. We investigated whether PTS was associated with global DNA methylation levels in the offspring.
Our sample was drawn from a birth cohort of women born between 1959 and 1963 in New York City (n = 90). We measured methylation of repetitive elements (Sat2, Alu, LINE-1) from peripheral blood granulocytes. We combined prospectively collected data on PTS with adult epidemiologic data and blood samples collected in 2001 to 2007 (mean age, 43 years). We used linear regression to assess the association between PTS and repetitive element methylation.
Thirty-six percent of mothers smoked during pregnancy. We observed an inverse association between PTS and Sat2 methylation. This inverse association remained even after adjustment for potential mediators including child environmental tobacco smoke exposure, birth size, postnatal weight and height changes, and adult smoking status and alcohol intake (β = -0.22, 95% confidence interval = -0.40 to -0.03 for ever exposed to PTS vs. never exposed using models of log-transformed methylation levels). PTS exposure was not statistically significantly associated with LINE-1 or Alu methylation.
PTS exposure, measured at the time of pregnancy and not retrospectively reported, was associated with a decrease in Sat2 methylation but not LINE-1 or Alu methylation.
If replicated in larger studies, this study supports a persistent effect of PTS on DNA methylation levels, as measured by Sat2, in adulthood.
接触产前烟草烟雾（PTS）与后代的许多健康结果有关，包括一些儿童癌症。基因组 DNA 低甲基化水平也与几种类型的癌症有关。我们调查了 PTS 是否与后代的整体 DNA 甲基化水平有关。
我们的样本取自纽约市 1959 年至 1963 年出生的女性的出生队列（n = 90）。我们测量了外周血粒细胞中重复元件（Sat2、Alu、LINE-1）的甲基化。我们将前瞻性收集的 PTS 数据与成人流行病学数据以及 2001 年至 2007 年收集的血液样本（平均年龄为 43 岁）相结合。我们使用线性回归来评估 PTS 与重复元件甲基化之间的关联。
36%的母亲在怀孕期间吸烟。我们观察到 PTS 与 Sat2 甲基化呈负相关。即使在调整了儿童环境烟草烟雾暴露、出生体重、产后体重和身高变化以及成人吸烟状况和饮酒量等潜在中介因素后，这种负相关仍然存在（β=-0.22，95%置信区间=-0.40 至-0.03，使用对数转化后的甲基化水平模型，暴露于 PTS 与从不暴露于 PTS）。PTS 暴露与 LINE-1 或 Alu 甲基化无统计学显著关联。
在怀孕期间测量而不是回顾性报告的 PTS 暴露与 Sat2 甲基化减少有关，但与 LINE-1 或 Alu 甲基化无关。
如果在更大的研究中得到复制，这项研究支持 PTS 对成年期 Sat2 测量的 DNA 甲基化水平的持续影响。
