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

被引:5
作者
Wang, Yi-Fan [1 ]
Li, Lei [1 ]
Deng, Xue-Qing [2 ]
Fang, Yu-Jing [3 ]
Zhang, Cai-Xia [1 ]
机构
[1] Sun Yat Sen Univ, Sch Publ Hlth, Dept Epidemiol, Guangzhou 510080, Peoples R China
[2] Sun Yat Sen Univ, Expt Teaching Ctr, Sch Publ Hlth, Guangzhou 510080, Peoples R China
[3] Sun Yat Sen Univ, Canc Ctr, Collaborat Innovat Ctr Canc Med, Canc Ctr ,Dept Expt Res,Collaborat Innovat Ctr Can, 651 Dongfeng Rd East, Guangzhou 510060, Peoples R China
关键词
Vitamin D metabolic pathway related genes; DNA methylation; VDR; Colorectal cancer; EPIGENETIC REGULATION; CYP24A1; EXPRESSION; MUCOSA; MARKER; SYSTEM; CYP2R1; CHINA; SERUM;
D O I
10.1186/s13148-023-01555-0
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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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页数:12
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