HIF3A DNA methylation, obesity and weight gain, and breast cancer risk among Mexican American women
HIF3A DNA methylation, obesity and weight gain, and breast cancer risk among Mexican American women
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DOI：
10.1016/j.orcp.2020.10.001
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发表时间：
2020-11-01
影响因子：
4.3
通讯作者：
Zhao, Hua
中科院分区：
文献类型：
--
作者：
Shen, Jie;Song, Renduo;Zhao, Hua
目的：在先前的全表观基因组关联研究中，缺氧诱导因子3α亚基（HIF3A）DNA甲基化已被报道与体重指数（BMI）和体重变化相关。然而，这些研究都没有纳入墨西哥裔美国人。
方法：在当前研究中，我们评估了从墨西哥裔美国人队列研究“Mano - A - Mano”中确定的927名墨西哥裔美国女性的HIF3A甲基化水平。
结果：与非肥胖女性相比，肥胖女性在三个CpG位点（位置46801557、46801642和46801699）的甲基化水平显著更高（P < 0.05）。此外，我们发现这三个CpG位点的甲基化水平升高与显著的体重增加相关（P < 0.05），体重增加定义为基线和随访之间BMI至少增加一个类别，中位随访时间为39个月。然后，使用诊断前的血液DNA样本，我们发现CpG 46801642处DNA甲基化增加与乳腺癌风险增加1.35倍相关（风险比（HR）= 1.35，95%置信区间（CI）：1.02，3.01），中位随访时间为127个月。利用癌症基因组图谱（TCGA）数据，我们进一步发现乳腺肿瘤中的HIF3A水平比正常组织甲基化程度显著更高且表达下调（两者P < 1×10⁻¹²）。
结论：因此，我们的结果提供了证据支持HIF3A在肥胖、体重增加和乳腺癌发展中的作用。（c）2020亚洲大洋洲肥胖研究协会。由爱思唯尔有限公司出版。保留所有权利。
Objective: In previous epigenome-wide association studies, Hypoxia inducible Factor 3 Alpha Subunit (HIF3A) DNA methylation has been reported to be associated with body mass index (BMI) and weight change. However, none of these studies have included Mexican Americans.Methods: In the current study, we assessed levels of HIF3A methylation in 927 Mexican American women identified from Mano-A-Mano, the Mexican American Cohort study.Results: Significantly higher methylation levels at three CpG sites (position 46801557, 46801642, and 46801699) were observed in obese women compared to non-obese women (P < 0.05). Furthermore, we found that elevated methylation levels at those three CpG sites were associated with significant weight gain (P < 0.05), defined as an increase in BMI by at least one category between the baseline and the followup, with a median follow-up time of 39 months. Then, using pre-diagnostic blood DNA samples, we found increased DNA methylation at CpG 46801642 to be associated with a 1.35-fold increased risk of breast cancer (Hazard Ratio (HR) = 1.35, 95% Confidence Interval (CI): 1.02, 3.01), with a median follow-up time of 127 months. Using the Cancer Genome Atlas (TCGA) data, we further found that levels of HIF3A were significantly higher-methylated and down-regulated in breast tumor than in normal tissues (P < 1 x 10(12) for both).Conclusion: Thus, our results provide evidence to support the role of HIF3A in obesity, weight gain, and the development of breast cancer. (c) 2020 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.