Molecular link(s) between hepatoblastoma pathogenesis and exposure to di-(2-ethylhexyl)phthalate: a hypothesis.

Hepatoblastoma (HB) is the most important primary liver cancer in children, accounting for up to 1% of all paediatric malignancies. It affects mostly infants and young children between the age of 6 months and 3 years. Predisposing genetic factors for HB have been identified and scientific evidence clearly points out HB as a multi-factorial condition based on both genetic and environmental factors. Nevertheless, a clear understanding of the pathogenesis is yet lacking. The present review will focus on the impact of exposure to environmental chemicals, such as di-(2-ethylhexyl)phthalate (DEHP), and recognized risk factors, such as intrauterine growth retardation (IUGR), on HB establishment via altered signalling pathways (Wnt and IGF). The hypothesis linking the impairment of IGF2 foetal/adult switching and exposure to DEHP is discussed as a way forward to support HB prevention and early diagnosis.