Department of Epidemiology, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
Experimental Teaching Center, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, China.
Clin Epigenetics. 2023 Aug 29;15(1):140. doi: 10.1186/s13148-023-01555-0.
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.
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.
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.
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.
维生素 D 可能具有抗肿瘤作用，其作用受到与维生素 D 代谢途径相关的基因的影响。表观遗传机制可能会影响维生素 D 代谢途径相关基因的表达水平，从而在结直肠癌的发生和发展中发挥重要作用。迄今为止，尚无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联。
本研究在中国广州开展了一项病例对照研究，共纳入 102 例结直肠癌病例和 102 例性别和年龄频数匹配的对照。通过 MethylTarget 测序选择 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）曲线评估 DNA 甲基化水平对结直肠癌的诊断价值。以最大 Youden 指数为界值点，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。采用多因素条件 Logistic 回归模型，在调整潜在混杂因素后，计算校正比值比（aOR）及其 95%置信区间（95%CI）。
在 153 个 CpG 位点中，8 个 CpG 位点在病例组和对照组之间存在显著差异。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（aOR，0.49；95%CI，0.26-0.91）。然而，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无显著关联。VDR 中显著 CpG 位点（aOR，0.28；95%CI，0.16-0.51）和 CYP24A1 中显著 CpG 位点（aOR，0.19；95%CI，0.09-0.40）的累积甲基化水平与结直肠癌风险呈显著负相关。CYP2R1 和 CYP27B1 中显著 CpG 位点的累积甲基化水平与结直肠癌风险之间无显著关联。
本研究表明，VDR 和 CYP24A1 中显著 CpG 位点的累积甲基化水平以及 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。
