血清代谢物在饮酒所致食管鳞状细胞癌中的中介效应

Mediation effect of serum metabolites on esophageal squamous cell carcinoma induced by alcohol consumption

目的 基于一项横断面研究探讨饮酒所致食管鳞状细胞癌(ESCC)发生通路中的潜在中介血清代谢物。方法 基于“国家食管癌早诊早治示范基地(山东省肥城市)”食管癌筛查平台,收集2013-07-23-2014-04-30(山东省肥城市)40~69岁参加筛查的农村居民为研究对象,并获得血清代谢谱、病理诊断和基线信息。多元logistic回归计算饮酒暴露对ESCC风险的OR值和95%CI。并采用高维中介分析和单因素中介分析筛选饮酒暴露导致ESCC的潜在中介代谢物。结果 共纳入463名研究对象,其中健康对照组250名,病例组213例(癌前病变192例,原位癌21例)。饮酒与ESCC风险增加1.973倍相关,OR=1.973,95%CI:1.049~3.769,P<0.001。通过高维中介分析筛选出4个代谢物作为中介变量,分别为PC(P-16:0/14:1)、组氨酸、门冬酰胺-苯丙氨酸和谷氨酰胺。单变量中介分析进一步证明了PC(P-16:0/14:1)、组氨酸和谷氨酰胺存在中介作用,中介比例分别为49.14%、58.14%和26.39%。结论 饮酒与ESCC事件有关,这一过程可能是由PC(P-16:0/14:1)、谷氨酰胺和组氨酸介导。

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.