Mycotoxin exposure is associated with increased risk of esophageal squamous cell carcinoma in Huaian area, China

Abstract

Background: Consumption of moldy food has previously been identified as a risk factor for esophageal squamous cell carcinoma (ESCC) in high-risk countries; however, what contributing roles these dietary carcinogenic mycotoxins play in the etiology of ESCC are largely unknown.

Methods: A mycotoxin biomarker-incorporated, population-based case-control study was performed in Huaian area, Jiangsu Province, one of the two high-risk areas in China. Exposure biomarkers of aflatoxins (AF) and fumonisins (FN) were quantitatively analyzed using HPLC-fluorescence techniques.

Results: Among the cases (n = 190), the median levels of AF biomarker, serum AFB₁-lysine adduct, and FN biomarker, urinary FB₁, were 1.77 pg/mg albumin and 176.13 pg/mg creatinine, respectively. Among the controls (n = 380), the median levels of AFB₁-lysine adduct and urinary FB₁ were 1.49 pg/mg albumin and 56.92 pg/mg creatinine, respectively. These mycotoxin exposure biomarker levels were significantly higher in cases as compared to controls (p < 0.05 and 0.01, respectively). An increased risk to ESCC was associated with exposure to both AFB₁ and FB₁ (p < 0.001 for both).

Conclusions: Mycotoxin exposure, especially to AFB₁ and FB₁, was associated with the risk of ESCC, and a greater-than-additive interaction between co-exposures to these two mycotoxins may contribute to the increased risk of ESCC in Huaian area, China.

Keywords: Aflatoxin B1; Co-exposure; Esophageal cancer; Fumonisin B1; Molecular epidemiology; Mycotoxins.

Fig. 1

Map of Huaian area, Jiangsu Province, China. Circled with arrow indicate the townships where the study participants were recruited for this case-control study. Map of Huaian was traced using Adobe Photoshop CS2 (https://www.adobe.com/), with texts and indicators added with Microsoft PowerPoint (https://www.microsoft.com/en-us/). No copyright issue present

Fig. 2

Comparison of biomarker levels between cases and controls. Plots depict overall levels of a urinary FB₁ and b serum AFB₁-lysine adducts in esophageal cancer case and control samples. Boxes in the plot represent 25 and 75 percentiles, with the medians as the middle lines. Bars represent 5 and 95 percentiles of data