The potential contribution of multiple mycotoxin exposure to esophageal cancer risk : insights from a case-control study in the Arsi-Bale districts, Ethiopia

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 largest 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. Several studies suggest that mycotoxin exposure may be a potential etiological factor for EC in the countries of the African EC belt [1]. In this work, we investigate mycotoxin exposure in a casecontrol 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 41 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. Evidence of mycotoxin exposure was observed in all plasma samples, with 10 different mycotoxins being detected in samples from cases, while only 6 different mycotoxins were detected in control samples. Ochratoxin A was detected in all cases and controls, while tenuazonic acid was detected in plasma of 145 (87.3%) cases and 71 (42.8%) controls. The absence of a mycotoxin regulatory policy in Ethiopia and low awareness of the study participants on mycotoxins may have contributed to chronic exposure to these mycotoxins. Ochratoxin A concentration in plasma was lower in cases than in controls (Mann–Whitney U test, p-value < 0.001), while in cases the concentration was higher for tenuazonic acid (p-value < 0.001), whose exposure has been described to cause the development of precancerous lesion on esophageal tissue in mice [2]. The mycotoxins citrinin, cyclopiazonic acid, deoxynivalenol, and zearalanone were detected in samples from both cases and controls with variable frequency (0.6 to 19.9%). Aflatoxin B2, enniatin B, nivalenol, and α-zearalenol were detected only in plasma from cases. Noteworthily, logistic regression analysis adjusting for confounders (age, gender) indicated that the probability of developing EC increased with increasing number of mycotoxin co-exposures (odds ratio 3.51, p-value < 0.001). This result emphasizes the need to characterize the effect of mycotoxin co-exposure as part of the exposome and include it in risk assessment, since currently mycotoxin safety levels do not consider the additive or synergistic effects of mycotoxin co-exposure.

Jaar van publicatie:2024

Toegankelijkheid:Closed