在埃塞俄比亚Oromia地区的Arsi-bale地区的食管癌病例对照研究中，通过人类生物监测进行多种霉菌毒素暴露评估

食管癌（EC）是一种恶性肿瘤，预后较差，五年生存率低于20％。它是全球第九次最常见的癌症，也是癌症相关死亡的第六个主要原因。 EC的发病率因地理而有很大差异，表明环境和生活方式因素以及疾病发作中的遗传因素的重要性。 In this work, we investigated mycotoxin exposure in a case-control study from the Arsi-Bale districts of Oromia regional state in Ethiopia, where there is a high incidence of EC while alcohol and tobacco use - two established risk factors for EC - are very rare.Internal exposure to 39 mycotoxins and metabolites was assessed by liquid chromatography-tandem mass spectrometry in plasma samples of EC cases （n = 166）和位置匹配的健康对照（n = 166），他们共有类似的饮食来源。使用结构化问卷收集人口统计学和生活方式数据。主成分分析和机器学习模型用于确定与EC相关的最相关的人口统计学，生活方式和霉菌毒素（共同）暴露变量。多元二元逻辑回归分析用于评估EC风险。在所有血浆样品中均观察到霉菌毒素暴露的证据，在EC病例的样品中检测到10种不同的霉菌毒素，而在健康对照组的样品中仅检测到6种不同的霉菌毒素。从所有病例和对照组中检测到血浆中的绿毒素A，而在145例（87.3％）病例和71例（42.8％）对照的血浆中检测到Tenuazonic酸。使用多变量的逻辑回归分析，暴露于tenuazonic酸（AOR = 1.88 [95％CI：1.68-2.11]）和多种霉菌毒素（AOR = 2.54 [95％CI：2.10-3.07]）与EC的正相关。病例在统计学上暴露于霉菌毒素的数量明显高于对照组。在研究人群中，暴露于Tenuazonic和多种霉菌毒素与EC的风险增加有关。 Although aflatoxin B1-lysine and the ratio of sphinganine to sphingosine (as a biomarker of effect to fumonisin exposure) were not assessed in this study, our result emphasizes the need to characterize the effect of mycotoxin co-exposure as part of the exposome and include it in risk assessment, since the current mycotoxin safety levels do not consider the additive or synergistic effects of mycotoxin共曝光。此外，在埃塞俄比亚EC的高发病率区域应考虑进行定期采样的前瞻性研究设计，以获得有关霉菌毒素暴露在疾病发作和发育中的作用的结论性结果。

Esophageal cancer (EC) is a malignancy with a poor prognosis and a five-year survival rate of less than 20%. It is the ninth most frequent cancer globally and the sixth leading cause of cancer-related deaths. The incidence of EC has been found to vary significantly by geography, indicating the importance of environmental and lifestyle factors along with genetic factors in the onset of the disease. In this work, we investigated mycotoxin exposure in a case-control study from the Arsi-Bale districts of Oromia regional state in Ethiopia, where there is a high incidence of EC while alcohol and tobacco use - two established risk factors for EC - are very rare.Internal exposure to 39 mycotoxins and metabolites was assessed by liquid chromatography-tandem mass spectrometry in plasma samples of EC cases (n = 166) and location-matched healthy controls (n = 166) who shared similar dietary sources. Demographic and lifestyle data were collected using structured questionnaires. Principal Component Analysis and machine learning models were used to identify the most relevant demographic, lifestyle, and mycotoxin (co-)exposure variables associated with EC. Multivariate binary logistic regression analysis was used to assess EC risk.Evidence of mycotoxin exposure was observed in all plasma samples, with 10 different mycotoxins being detected in samples from EC cases, while only 6 different mycotoxins were detected in samples from healthy controls. Ochratoxin A was detected in plasma from all cases and controls, while tenuazonic acid was detected in plasma of 145 (87.3%) cases and 71 (42.8%) controls. Using multivariable logistic regression analysis, exposure to tenuazonic acid (AOR = 1.88 [95% CI: 1.68-2.11]) and to multiple mycotoxins (AOR = 2.54 [95% CI: 2.10-3.07]) were positively associated with EC.All cases and controls were exposed to at least one mycotoxin. Cases were exposed to a statistically significantly higher number of mycotoxins than controls. Exposure to tenuazonic acid and to multiple mycotoxins were associated with increased risk of EC in the study population. Although aflatoxin B1-lysine and the ratio of sphinganine to sphingosine (as a biomarker of effect to fumonisin exposure) were not assessed in this study, our result emphasizes the need to characterize the effect of mycotoxin co-exposure as part of the exposome and include it in risk assessment, since the current mycotoxin safety levels do not consider the additive or synergistic effects of mycotoxin co-exposure. Moreover, a prospective study design with regular sampling should be considered in this high incidence area of EC in Ethiopia to obtain conclusive results on the role of mycotoxin exposure in the onset and development of the disease.