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Childhood Liver Cancer Treatment (PDQ®): Treatment - Health Professional Information [NCI] - General Information

Table 1. Risk Factors Associated With Hepatoblastoma and Hepatocellular Carcinoma continued...

All children with Beckwith-Wiedemann syndrome or isolated hemihyperplasia should be screened regularly by ultrasound to detect abdominal malignancies at an early stage.[29] Screening using alpha-fetoprotein (AFP) levels, in addition to abdominal ultrasound, has helped in the early detection of hepatoblastoma in children with Beckwith-Wiedemann syndrome or hemihyperplasia.[33] Other somatic overgrowth syndromes, such as Simpson-Golabi-Behmel syndrome, may also be associated with hepatoblastoma.[34]

Familial adenomatous polyposis

There is an association between hepatoblastoma and familial adenomatous polyposis (FAP); children in families that carry the APC gene are at an 800-fold increased risk for hepatoblastoma. However, hepatoblastoma has been reported to occur in less than 1% of FAP family members, so ultrasound and AFP screening for hepatoblastoma in members of families with FAP has been controversial.[17,18,19,35]

A study of 50 sequential children with apparent sporadic hepatoblastoma reported five children (10%) had APC mutations.[35] Data to date cannot rule out the possibility that predisposition to hepatoblastoma may be limited to a specific subset of APC mutations. Another study of children with hepatoblastoma found a predominance of the mutation in the 5' region of the gene, but some patients had mutations closer to the 3' region.[36] Perhaps, screening children with hepatoblastoma for APC mutations may be appropriate, as they should be followed for potential colon cancer. This preliminary study provides some evidence that screening children with hepatoblastoma for APC mutations may be appropriate.

In the absence of APC germline mutations, childhood hepatoblastomas do not have somatic mutations in the APC gene; however, they frequently have mutations in the beta-catenin gene, the function of which is closely related to APC.[37]

Hepatitis B and hepatitis C infection

Hepatocellular carcinoma is associated with hepatitis B and hepatitis C infection in adults,[21,22,23] while in children there is an association with perinatally acquired hepatitis B virus. Widespread hepatitis B immunization has decreased the incidence of hepatocellular carcinoma in Asia.[9] Compared with adults, the incubation period from hepatitis virus infection to the genesis of hepatocellular carcinoma is extremely short in a small subset of children with perinatally acquired virus. Mutations in the met/hepatocyte growth factor receptor gene occur in childhood hepatocellular carcinoma, and this could be one mechanism that results in a shortened incubation period. Hepatitis C infection is associated with development of cirrhosis and hepatocellular carcinoma that takes decades to develop and is generally not seen in children.[38]

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