Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Clin Epigenetics. 2024 Nov 25;16(1):168. doi: 10.1186/s13148-024-01774-z.
Transportation noise has been linked with breast cancer, but existing literature is conflicting. One proposed mechanism is that transportation noise disrupts sleep and the circadian rhythm. We investigated the relationships between road traffic noise, DNA methylation in circadian rhythm genes, and breast cancer. We selected 610 female participants (318 breast cancer cases and 292 controls) enrolled into the Malmö, Diet, and Cancer cohort. DNA methylation of CpGs (N = 29) in regulatory regions of circadian rhythm genes (CRY1, BMAL1, CLOCK, and PER1) was assessed by pyrosequencing of DNA from lymphocytes collected at enrollment. To assess associations between modeled 5-year mean residential road traffic noise and differentially methylated CpG positions, we used linear regression models adjusting for potential confounders, including sociodemographics, shiftwork, and air pollution. Linear mixed effects models were used to evaluate road traffic noise and differentially methylated regions. Unconditional logistic regression was used to investigate CpG methylation and breast cancer.
We found that higher mean road traffic noise was associated with lower DNA methylation of three CRY1 CpGs (CpG1, CpG2, and CpG12) and three BMAL1 CpGs (CpG2, CpG6, and CpG7). Road traffic noise was also associated with differential methylation of CRY1 and BMAL1 promoters. In CRY1 CpG2 and CpG5 and in CLOCK CpG1, increasing levels of methylation tended to be associated with lower odds of breast cancer, with odds ratios (OR) of 0.88 (95% confidence interval (CI) 0.76-1.02), 0.84 (95% CI 0.74-0.96), and 0.80 (95% CI 0.68-0.94), respectively.
In summary, our data suggest that DNA hypomethylation in CRY1 and BMAL1 could be part of a causal chain from road traffic noise to breast cancer. This is consistent with the hypothesis that disruption of the circadian rhythm, e.g., from road traffic noise exposure, increases the risk of breast cancer. Since no prior studies have explored this association, it is essential to replicate our results.
交通噪声与乳腺癌有关，但现有文献存在争议。一个提出的机制是交通噪声扰乱了睡眠和昼夜节律。我们研究了道路交通噪声、昼夜节律基因的 DNA 甲基化与乳腺癌之间的关系。我们选择了 610 名女性参与者（318 名乳腺癌病例和 292 名对照）纳入马尔默、饮食和癌症队列。通过对淋巴细胞中 DNA 进行焦磷酸测序，评估了生物钟基因（CRY1、BMAL1、CLOCK 和 PER1）调节区域中 29 个 CpG（N=29）的 DNA 甲基化情况。为了评估 5 年平均居住道路交通噪声与差异甲基化 CpG 位置之间的关联，我们使用线性回归模型调整了潜在混杂因素，包括社会人口统计学、轮班工作和空气污染。线性混合效应模型用于评估道路交通噪声和差异甲基化区域。使用无条件逻辑回归研究 CpG 甲基化与乳腺癌之间的关系。
我们发现，较高的平均道路交通噪声与三个 CRY1 CpG（CpG1、CpG2 和 CpG12）和三个 BMAL1 CpG（CpG2、CpG6 和 CpG7）的 DNA 甲基化水平降低有关。道路交通噪声也与 CRY1 和 BMAL1 启动子的差异甲基化有关。在 CRY1 CpG2 和 CpG5 以及 CLOCK CpG1 中，随着甲基化水平的增加，乳腺癌的患病几率呈下降趋势，比值比（OR）分别为 0.88（95%置信区间（CI）0.76-1.02）、0.84（95% CI 0.74-0.96）和 0.80（95% CI 0.68-0.94）。
总之，我们的数据表明，CRY1 和 BMAL1 中的 DNA 低甲基化可能是道路交通噪声导致乳腺癌的因果链的一部分。这与昼夜节律中断的假设一致，例如，由于道路交通噪声暴露，增加了乳腺癌的风险。由于之前没有研究探索过这种关联，因此复制我们的结果至关重要。
