已有研究表明，维生素B12缺乏与食管癌前病变（EPL）相关。然而，其潜在机制目前尚不清楚。本研究旨在评估维生素B12及其调控的表观遗传修饰在EPL中的作用，并初步提供有关EPL早期预测潜在分子标志物的信息。我们从食管癌早期诊断和早期治疗项目数据库中收集了200例EPL患者和200例配对对照的信息和样本。比较了维生素B12、一碳代谢标志物、TCN2 C776G的遗传多态性和DNA甲基化。进一步通过定向亚硫酸盐测序验证了初步确定的甲基化CpG位点差异的候选启动子。结果显示，与对照组相比，EPL患者血清中维生素B12和转钴胺II水平显著降低，同高同型半胱氨酸和5-甲基四氢叶酸水平显著升高。发现TCN2 C776G多态性与EPL易感性有关，并可能与维生素B12的营养状况相互作用，影响男性主体的EPL风险。此外，观察到维生素B12缺乏与全局低甲基化相关，以及UGT2B15和FGFR2启动子区域特异性高甲基化。本研究提示，维生素B12缺乏可能通过一碳代谢途径与异常DNA甲基化和EPL风险增加相关；TCN2 C776G多态性可能与维生素B12的营养状况相互作用，影响男性主体的EPL风险；并且确定了UGT2B15和FGFR2启动子中具有潜在作为有希望的分子标志物的特定位置。版权所有 © 2023 Elsevier Inc. 发表。

Vitamin B12 depletion has been suggested to be associated with esophageal precancerous lesions (EPL). However, the potential mechanisms remain unclear.This study aims to evaluate the role of vitamin B12 and its regulated epigenetic modification in EPL and provide preliminary information on the identification of potential molecular biomarkers for the early prediction of EPL.We collected information and samples from the Early Diagnosis and Early Treatment Project of Esophageal Cancer database from 200 EPL cases and 200 matched controls. Vitamin B12, one-carbon metabolism biomarkers, genetic polymorphism of TCN2 C776G, and DNA methylation were compared. Preliminarily identified candidate promoters of differentially methylated CpG positions were further verified by targeted bisulfite sequencing.EPL cases had significantly lower serum levels of vitamin B12 and transcobalamin II, and higher serum levels of homocysteine and 5-methyltetrahydrofolate than controls. The TCN2 C776G polymorphism was found to be associated with susceptibility to EPL and may interact with vitamin B12 nutritional status to influence the risk of EPL in male subjects. In addition, global hypomethylation related to vitamin B12 depletion was observed in EPL cases, along with region-specific hypermethylation of UGT2B15 and FGFR2 promoters.This study suggests that vitamin B12 depletion may be associated with aberrant DNA methylation and increased risk of EPL through the one-carbon metabolism pathway, presents that the TCN2 C776G polymorphism may interact with vitamin B12 nutritional status to affect EPL risk in males, and also identifies specific locations in the UGT2B15 and FGFR2 promoters with potential as promising molecular biomarkers.Copyright © 2023. Published by Elsevier Inc.