维生素D代谢途径相关基因的DNA甲基化与结直肠癌风险的关系

IF 5.7 2区 医学 Q1 Medicine Clinical Epigenetics Pub Date : 2023-08-29 DOI:10.1186/s13148-023-01555-0
Yi-Fan Wang, Lei Li, Xue-Qing Deng, Yu-Jing Fang, Cai-Xia Zhang
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引用次数: 0

摘要

背景:维生素D可能具有抗肿瘤作用,其作用受维生素D代谢途径相关基因的影响。表观遗传机制可能影响维生素D代谢途径相关基因的表达水平,从而在结直肠癌的发生发展中发挥重要作用。迄今为止,还没有研究报道血液中维生素D代谢途径相关基因的DNA甲基化水平与结直肠癌风险之间的关系。方法:对广州102例结直肠癌患者和102例性别、年龄、频率匹配的对照组进行病例对照研究。选择VDR、CYP24A1、CYP27B1和CYP2R1基因中的CpG岛进行DNA甲基化分析。采用受试者工作特征(ROC)曲线评价DNA甲基化水平对结直肠癌的诊断价值。以约登指数最大的点为边界值,将维生素D代谢途径相关基因的累积甲基化水平分为低甲基化和高甲基化。在对潜在混杂因素进行校正后,采用无条件多变量逻辑回归模型计算校正优势比(aOR)和95%置信区间(95% ci)。结果:153个CpG位点中,8个CpG位点与对照组有显著性差异。CYP2R1中所有CpG位点的累积甲基化水平与结直肠癌的风险呈负相关(aOR, 0.49;95% ci, 0.26-0.91)。然而,未发现VDR、CYP24A1和CYP27B1中所有CpG位点的累积甲基化水平与结直肠癌风险之间存在显著关联。VDR中重要CpG位点的累积甲基化水平显著负相关(aOR, 0.28;95% CI, 0.16-0.51)和CYP24A1 (aOR, 0.19;95% CI, 0.09-0.40)和结直肠癌风险。CYP2R1和CYP27B1中重要CpG位点的累积甲基化水平与结直肠癌风险之间没有显著关联。结论:本研究表明,VDR和CYP24A1中重要CpG位点以及CYP2R1中所有CpG位点的累积甲基化水平与结直肠癌风险呈负相关。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Association of DNA methylation of vitamin D metabolic pathway related genes with colorectal cancer risk.

Background: Vitamin D might have anti-tumor effect, which is affected by the genes related to vitamin D metabolic pathway. Epigenetic mechanism may affect the expression level of vitamin D metabolic pathway related genes, then plays an important role in the occurrence and development of colorectal cancer. To date, no study has reported on the association between blood-based DNA methylation level of vitamin D metabolic pathway related genes and colorectal cancer risk.

Methods: A case-control study was conducted including 102 colorectal cancer cases and 102 sex- and age-frequency-matched controls in Guangzhou, China. CpG islands in the VDR, CYP24A1, CYP27B1 and CYP2R1 genes were chosen for DNA methylation analysis by MethylTarget sequencing. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of DNA methylation levels for colorectal cancer. Taking the point with the largest Youden index as the boundary value, the cumulative methylation levels of vitamin D metabolic pathway related genes were divided into hypomethylation and hypermethylation. Unconditional multivariable logistical regression model was used to calculate the adjusted odds ratio (aOR) and 95% confidence intervals (95% CIs) after adjusting for potential confounders.

Results: Among 153 CpG sites, 8 CpG sites were significantly different between the cases and the controls. The cumulative methylation level of all CpG sites in CYP2R1 was inversely associated with the risk of colorectal cancer (aOR, 0.49; 95% CI, 0.26-0.91). However, no significant association was found between cumulative methylation levels of all CpG sites in VDR, CYP24A1 and CYP27B1 and colorectal cancer risk. Significant inverse association was observed between cumulative methylation level of significant CpG sites in VDR (aOR, 0.28; 95% CI, 0.16-0.51) and CYP24A1 (aOR, 0.19; 95% CI, 0.09-0.40) and colorectal cancer risk. There were no significant associations between cumulative methylation levels of significant CpG sites in CYP2R1 and CYP27B1 and colorectal cancer risk.

Conclusions: This study indicated that the cumulative methylation levels of significant CpG sites in VDR and CYP24A1 and all CpG sites in CYP2R1 were inversely associated with colorectal cancer risk.

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来源期刊
Clinical Epigenetics
Clinical Epigenetics Biochemistry, Genetics and Molecular Biology-Developmental Biology
CiteScore
8.90
自引率
5.30%
发文量
150
审稿时长
12 weeks
期刊介绍: Clinical Epigenetics, the official journal of the Clinical Epigenetics Society, is an open access, peer-reviewed journal that encompasses all aspects of epigenetic principles and mechanisms in relation to human disease, diagnosis and therapy. Clinical trials and research in disease model organisms are particularly welcome.
期刊最新文献
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