食管癌（EC）是一种预后较差的恶性肿瘤，五年生存率低于20%。它是全球第九大常见癌症，也是癌症相关死亡的第六大原因。研究发现，EC 的发病率因地理位置而异，表明环境和生活方式因素以及遗传因素在该疾病发病中的重要性。在这项工作中，我们通过一项病例对照研究调查了埃塞俄比亚奥罗米亚州 Arsi-Bale 地区的霉菌毒素暴露情况，该地区 EC 发病率很高，而饮酒和吸烟（两个已确定的 EC 危险因素）则非常严重。罕见。通过液相色谱-串联质谱法对具有相似饮食来源的 EC 病例 (n = 166) 和位置匹配的健康对照 (n = 166) 的血浆样本进行了 39 种霉菌毒素和代谢物的内部暴露评估。使用结构化问卷收集人口统计和生活方式数据。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、生活方式和霉菌毒素（共同）暴露变量。采用多变量二元logistic回归分析来评估EC风险。在所有血浆样本中均观察到霉菌毒素暴露的证据，在EC病例的样本中检测到10种不同的霉菌毒素，而在健康对照的样本中仅检测到6种不同的霉菌毒素。所有病例和对照者的血浆中均检测到了赭曲霉毒素 A，而 145 例（87.3%）例患者和 71 例（42.8%）对照者的血浆中检测到了丁苯酸。使用多变量逻辑回归分析，接触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呈正相关。所有病例对照组暴露于至少一种霉菌毒素。病例接触的霉菌毒素数量在统计学上显着高于对照组。在研究人群中，接触tenuazonic Acid和多种霉菌毒素与EC风险增加相关。尽管本研究中未评估黄曲霉毒素 B1-赖氨酸以及二氢鞘氨醇与鞘氨醇的比率（作为伏马菌素暴露影响的生物标志物），但我们的结果强调需要表征霉菌毒素共同暴露作为暴露组的一部分的影响，并包括在风险评估中，由于目前的霉菌毒素安全水平没有考虑霉菌毒素共同暴露的累加或协同效应。此外，应考虑在埃塞俄比亚这一 EC 高发地区进行定期抽样的前瞻性研究设计，以获得有关霉菌毒素暴露在疾病发生和发展中的作用的结论性结果。版权所有 © 2024。由 Elsevier GmbH 出版。

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.Copyright © 2024. Published by Elsevier GmbH.