Background

We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors.

Methods

We conducted a study of women enrolled in the Western New York Exposures and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and when she had her first child was estimated. TE exposure was modeled for each woman's residence at menarche, her first birth, and twenty and ten years prior to diagnosis. Unconditional logistic regression was employed to estimate odds ratios (OR) of having methylation greater than the median value, adjusting for age, secondhand smoke exposure before age 20, current smoking status, and estrogen receptor status.

Results

Exposure to higher TSP at a woman's first birth was associated with lower methylation of SCGB3A1 (OR = 0.48, 95% CI: 0.23–0.99) and higher methylation of SYK (OR = 1.86, 95% CI: 1.03–3.35). TE at menarche was associated with increased methylation of SYK (OR = 2.37, 95% CI: 1.05–5.33). TE at first birth and ten years prior to diagnosis was associated with decreased methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95% CI: 0.26–0.89). Although these associations were nominally significant, none were significant after adjustment for multiple comparisons (p < 0.01).

Conclusions

We observed suggestive evidence that exposure to ambient air pollution throughout life, measured as TSP and TE, may be associated with DNA methylation of some tumor suppressor genes in breast tumor tissue. Future studies with a larger sample size that assess methylation of more sites are warranted.

中文翻译：

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终生暴露于环境空气污染和乳腺癌中抑癌基因的甲基化

背景

我们之前曾报道过，通过暴露于空气污染的两种测量方法，与总的悬浮颗粒物（TSP）和交通排放量（TE）以及暴露于多环芳烃（PAHs）的可能代理关系，可以提高与早期生命接触相关的乳腺癌风险。研究表明，暴露于PAHs与健康个体外周血中DNA甲基化的异常模式有关。暴露于乳腺肿瘤组织中的PAHs和甲基化反应很少受到关注。我们检查了早期暴露于TSP和TE与乳腺癌中DNA甲基化模式的关系。

方法

我们对参加纽约西部暴露和乳腺癌（WEB）研究的妇女进行了一项研究。使用基于亚硫酸氢盐的焦磷酸测序评估了九个基因（SFN，SCGB3A1，RARB，GSTP1，CDKN2A CCND2，BRCA1，FHIT和SYK）的甲基化。估计每个妇女在出生，初潮和生下第一个孩子时的家庭住所中的TSP暴露量。针对每个妇女在月经初潮时的住所，她的第一胎以及诊断前的二十十年建模了TE暴露。采用无条件逻辑回归来估计甲基化大于中值的比值比（OR），并根据年龄，20岁之前的二手烟暴露量，当前吸烟状况和雌激素受体状况进行调整。

结果

在妇女的第一胎中，较高的TSP暴露与SCGB3A1的甲基化程度较低（OR = 0.48，95％CI：0.23-0.99）和SYK的甲基化程度较高（OR = 1.86，95％CI：1.03-3.35）有关。月经初潮时的TE与SYK的甲基化增加有关（OR = 2.37，95％CI：1.05-5.33）。第一胎和诊断前十年的TE与CCND2甲基化降低有关（或诊断前十年= 0.48，95％CI：0.26-0.89）。尽管这些关联在名义上是显着的，但在进行多次比较调整后，均无显着意义（p <0.01）。

结论

我们观察到提示性的证据，即一生中暴露于环境空气污染（以TSP和TE衡量）可能与乳腺肿瘤组织中某些抑癌基因的DNA甲基化有关。将来需要进行更大样本量的评估更多位点甲基化的研究。