It is hypothesized that esophageal precancerous lesions (EPLs) have a surge requirement for coenzyme I (NAD). The purpose of this study is to clarify the key control points of NAD synthesis in developing EPL by detecting related markers and the gene polymorphism of NAD synthesis and metabolism. This case–control study was conducted in Huai’an, China. In total, 100 healthy controls and 100 EPL cases matched by villages, gender, and age (±2 years) were included. The levels of plasma niacin and nicotinamide, and the protein concentration of NAMPT, NAPRT, and PARP-1 were quantitatively analyzed. PARP-1 gene polymorphism was detected to determine if the cases differed genetically in NAD synthesis. The levels of plasma niacin and nicotinamide and the concentrations of NAMPT were not related to the risk of EPL, but the over-expressions of NAPRT (p = 0.014, 0.001, and 0.016, respectively) and PARP-1 (p for trend = 0.021) were associated with the increased EPL risk. The frequency distribution of APRP-1 genotypes was found to not differ between the two groups, while the EPL group showed an increased frequency of the variant C allele. NAPRT, but not NAMPT, was found to be responsible for the stress of excess NAD synthesis in EPL. Focusing on the development of NAPRT inhibitors may be beneficial to prevent and control ESCC.

The role of selenium in the developmental process of esophageal cancer (EC) requires further investigation. To explore the relationship between selenium-related factors and EC through bioinformatic analysis, a case-control study was conducted to verify the results. Utilizing the GEPIA and TCGA databases, we delineated the differential expression of glutathione peroxidase 3 (GPx3) in EC and normal tissues, identified differentially expressed genes (DEGs), and a performed visualization analysis. Additionally, 100 pairs of dietary and plasma samples from esophageal precancerous lesions (EPLs) of esophageal squamous cancer (ESCC) cases and healthy controls from Huai’an district, Jiangsu, were screened. The levels of dietary selenium, plasma selenium, and related enzymes were analyzed using inductively coupled plasma mass spectrometry (ICP-MS) or ELISA kits. The results showed lower GPx3 expression in tumor tissues compared to normal tissues. Further analysis revealed that DEGs were mainly involved in the fat digestion and absorption pathway, and the core protein fatty acid binding protein 1 (FABP1) was significantly upregulated and negatively correlated with GPx3 expression. Our case-control study found that selenium itself was not associated with EPLs risk. However, both the decreased concentration of GPx3 and the increase in FABP1 were positively correlated with the EPLs risk (p for trend = 0.035 and 0.046, respectively). The different expressions of GPx3 and FABP1 reflect the potential of selenium for preventing ESCC at the EPLs stage. GPx3 may affect EC through FABP1, which remains to be further studied.