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.
Salvatore
Marco
M
Department of Cell Biology and Neurosciences, National Centre for Rare Diseases, Rome, Italy.
Lorenzetti
Stefano
S
Maranghi
Francesca
F
Mantovani
Alberto
A
Taruscio
Domenica
D
D000818:Animals; D002675:Child, Preschool; D004051:Diethylhexyl Phthalate / Q000009:adverse effects*; D004781:Environmental Exposure; D005260:Female; D005317:Fetal Growth Retardation / Q000503:physiopathology; D018197:Hepatoblastoma / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007223:Infant; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012307:Risk Factors; D015398:Signal Transduction; D051155:Wnt1 Protein / Q000235:genetics / Q000378:metabolism; D000509:alpha-Fetoproteins / Q000187:drug effects; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
D051155:Wnt1 Protein; D000509:alpha-Fetoproteins; D051176:beta Catenin; D007335:Insulin-Like Growth Factor II; D004051:Diethylhexyl Phthalate