维生素D可能具有抗肿瘤作用，其受与维生素D代谢途径相关的基因的影响。表观遗传机制可能影响维生素D代谢途径相关基因的表达水平，进而在结直肠癌的发生和发展中起重要作用。迄今为止，没有研究报道了与维生素D代谢途径相关基因血液DNA甲基化水平与结直肠癌风险之间的关联。在中国广州进行了一项病例对照研究，包括102例结直肠癌病例和102名性别和年龄频率匹配的对照。选择VDR、CYP24A1、CYP27B1和CYP2R1基因中的CpG岛进行DNA甲基化分析。接受者操作特征曲线（ROC曲线）用于评估DNA甲基化水平对结直肠癌的诊断价值。以具有最大Youden指数的点作为边界值，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。在调整潜在混杂因素后，使用无条件多元逻辑回归模型计算调整后的比值比（aOR）和95％置信区间（95％ CI）。在153个CpG位点中，有8个CpG位点在病例和对照之间显著不同。 CYP2R1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，在VDR、CYP24A1和CYP27B1的所有CpG位点的累积甲基化水平与结直肠癌风险之间没有发现显著关联。VDR和CYP24A1显著CpG位点的累积甲基化水平与结直肠癌风险呈负相关。在CYP2R1和CYP27B1的显著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。本研究表明，VDR和CYP24A1的显著CpG位点的累积甲基化水平以及CYP2R1的所有CpG位点的累积甲基化水平与结直肠癌风险呈负相关。© 2023. BioMed Central Ltd., part of Springer Nature.

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.© 2023. BioMed Central Ltd., part of Springer Nature.