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

Folia Med (Plovdiv). 2008 Oct-Dec;50(4):17-23.

Abstract

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Child, Preschool
  • Diethylhexyl Phthalate / adverse effects*
  • Environmental Exposure
  • Female
  • Fetal Growth Retardation / physiopathology
  • Hepatoblastoma / chemically induced*
  • Hepatoblastoma / genetics
  • Hepatoblastoma / metabolism
  • Humans
  • Infant
  • Insulin-Like Growth Factor II / genetics
  • Insulin-Like Growth Factor II / metabolism
  • Liver Neoplasms / chemically induced*
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Risk Factors
  • Signal Transduction
  • Wnt1 Protein / genetics
  • Wnt1 Protein / metabolism
  • alpha-Fetoproteins / drug effects
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • Wnt1 Protein
  • alpha-Fetoproteins
  • beta Catenin
  • Insulin-Like Growth Factor II
  • Diethylhexyl Phthalate