In Peru, we have identified a distinct type of hepatocellular carcinoma (HCC) that deviates from typical presentations seen elsewhere. Notably, HCC affects a significant proportion of children, adolescents, and young adults—an occurrence that is exceptional globally. The age distribution of HCC cases in Peru is bimodal, indicating different tumor processes in these two patient groups.
The primary risk factor for HCC, chronic hepatitis B virus (HBV) infection, shows unique characteristics in Peru. Patients with HCC exhibit low viral DNA loads (approximately 80 copies/mL), which differs from patterns observed in other regions where carcinogenesis is correlated with high viral loads. Additionally, the molecular alterations in Peruvian tumors contrast sharply with those found in Europe and Asia, with particularly low mutation rates for TERT, TP53, and CTNNB1 (5-15%). While HCC globally exhibits DNA hypomethylation, Peruvian liver tumors demonstrate high levels of DNA methylation affecting a significant number of CpG islands.
Our recent study indicates that Peruvian populations are more heavily exposed to a range of pesticides compared to those in Europe (specifically France) and the Far East. Research has suggested that pesticide exposure may significantly impact both the environment and the health of humans and animals in Peru. Two specific classes of substances of interest are endocrine-disrupting pesticides with insecticidal activity (ED) and succinate dehydrogenase inhibitors (SDHi) with fungicidal properties. Notably, the fungicide boscalid (an SDHi) was detected in many participants. Although SDHi are not currently recognized as carcinogenic, their mechanism of action leads to succinate accumulation—a normal product of the mitochondrial Krebs cycle that also acts as an oncometabolite. Succinate inhibits TET and KDM-JMJ enzymes, which are crucial for DNA and histone demethylation.
Our project aims to investigate whether certain classes of pesticides, particularly S
