Circulating Aflatoxin B1-Related TP53 Mutation Detected by Digital PCR in Tunisian Patients with and Without Hepatocellular Carcinoma

Background: In the recent years, hepatocellular carcinoma (HCC) has become one of the first causes of cancer mortality in humans. Among the issues explaining this appalling situation the lack of early biomarkers occupies a prominent position. In patients with tumors, free circulating DNA originating from tumor cells represents a promising material for the early detection of the disease. In HCC, two mutations, R249S on TP53 and -124C>T in TERT promoter, are potentially present in large subsets of patients and could be considered as good candidate biomarkers. Tunisia is a subtropical country where persistent infections with hepatitis virus represent a significant burden of diseases and food contamination with mycotoxins has been consistently detected. Methods: In a pilot study, using the droplet digital PCR (ddPCR) technique, blood samples from 47 patients with HCC and 51 control individuals were evaluated for the presence of the TP53 or TERT mutants in the bloodstream. Results: We observed that 19.1% and 14.9% of the patients with HCC were carrying TP53 or TERT mutants, while 47.1% and 5.8% of controls were positive for the same biomarkers (P = 0.005 and P = 0.18, ns). Most (66.6%) HCC patients with TP53 R49S were coming from the region of Nabeul (North East). Conclusions: This preliminary analysis indicates that droplet digital might be useful for the diagnosis of HCC or screening high-risk subjects in the North African context. In addition, our results confirm previous data obtained by foodstuffs analyses suggesting that a sizeable proportion of the middle-aged Tunisian population is or has been significantly exposed to aflatoxin B1. Larger studies are now mandatory to confirm and refine these preliminary data.