Department of Cancer Epidemiology and Prevention Research, CancerControl Alberta, Alberta Health Services, Calgary, Alberta, Canada.
Department of Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada.
PLoS One. 2018 Jun 28;13(6):e0198641. doi: 10.1371/journal.pone.0198641. eCollection 2018.
Physical activity is associated with a lower risk of breast, colon, and endometrial cancer. Epigenetic mechanisms such as changes in DNA methylation may help to explain these protective effects. We assessed the impact of a one year aerobic exercise intervention on DNA methylation biomarkers believed to play a role in carcinogenesis. The Alberta Physical Activity and Breast Cancer Prevention (ALPHA) Trial was a two-armed randomized controlled trial in 320 healthy, inactive, postmenopausal women with no history of cancer. In an ancillary analysis, frozen blood samples (n = 256) were reassessed for levels of DNA methylation within LINE-1 and Alu repeats as well as within the promoter regions of APC, BRCA1, RASSF1, and hTERT genes. Differences between the exercise and control arm at 12-months, after adjusting for baseline values, were estimated within an intent-to-treat and per-protocol analysis using linear regression. No significant differences in DNA methylation between the exercise and control arms were observed. In an exploratory analysis, we found that the prospective change in estimated VO2max was negatively associated with RASSF1 methylation in a dose-response manner (p-trend = 0.04). A year-long aerobic exercise intervention does not affect LINE-1, Alu, APC, BRCA1, RASSF1, or hTERT methylation in healthy, inactive, postmenopausal women. Changes in DNA methylation within these genomic regions may not mediate the association between physical activity and cancer in healthy postmenopausal women. Additional research is needed to validate our findings with RASSF1 methylation.
ClinicalTrials.gov NCT00522262.
身体活动与较低的乳腺癌、结肠癌和子宫内膜癌风险相关。表观遗传机制，如 DNA 甲基化的变化，可能有助于解释这些保护作用。我们评估了为期一年的有氧运动干预对被认为在致癌作用中起作用的 DNA 甲基化生物标志物的影响。艾伯塔省身体活动与乳腺癌预防（ALPHA）试验是一项在 320 名健康、不活跃、绝经后且无癌症病史的女性中进行的双臂随机对照试验。在一项辅助分析中，对冷冻血样（n=256）进行了重新评估，以检测 LINE-1 和 Alu 重复序列以及 APC、BRCA1、RASSF1 和 hTERT 基因启动子区域内的 DNA 甲基化水平。在意向治疗和方案分析中，通过线性回归，在调整基线值后，估计了 12 个月时锻炼组和对照组之间的差异。在锻炼组和对照组之间未观察到 DNA 甲基化的显著差异。在一项探索性分析中，我们发现，估计的 VO2max 的前瞻性变化与 RASSF1 甲基化呈剂量反应关系呈负相关（p 趋势=0.04）。为期一年的有氧运动干预不会影响健康、不活跃、绝经后女性的 LINE-1、Alu、APC、BRCA1、RASSF1 或 hTERT 甲基化。这些基因组区域内 DNA 甲基化的变化可能不会介导身体活动与健康绝经后妇女癌症之间的关联。需要进一步的研究来验证我们关于 RASSF1 甲基化的发现。
ClinicalTrials.gov NCT00522262。
