血清代谢物在饮酒所致食管鳞状细胞癌中的中介效应

Objective: A cross-sectional study was conducted to investigate the potential mediating serum metabolites in the pathways of alcohol-induced esophageal squamous cell carcinoma (ESCC) occurrence. Methods: In this study, participants were rural residents aged 40 to 69 years who participated in the screening program on the national esophageal cancer early diagnosis and early treatment demonstration base (City of Feicheng, Shandong, China) between July 23, 2013 and April 30, 2014. Serum metabolic profiles, pathological diagnosis and baseline information of participants were obtained. Multiple logistic regression was used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of alcohol drinking exposure to ESCC risk. High-dimensional mediation analysis and univariate mediation analysis were performed to screen potential intermediate metabolites of alcohol drinking exposure for ESCC. Results: A total of 463 subjects were enrolled, including 250 in the control group and 213 in the case group (precancerous lesions: 192, tumor in situ:21).Alcohol drinking was associated with a 1.973-fold increase of ESCC risk (OR=1.973, 95%CI:1.049-3.769). A total of 4 metabolites were screened as mediators by high-dimensional mediation analysis, including PC(P-16:0/14:1), histidine, asparagine-phenylalanine and glutamine. In addition, PC(P-16:0/14:1), glutamine, and histidine were further proven existing mediation effects according to univariate mediation analysis. And the proportions of mediation of them were 49.14%, 58.14% and 26.39%, respectively. Conclusion: Our findings suggest that cigarette smoking contributed to incident ESCC, which may be mediated by PC(P-16:0/14:1), glutamine, and histidine.