Abstract
Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with more than 80% of cases found in endemic areas of hepatitis B such as Africa or East Asia. A family history of liver cancer increases HCC risk, independently of hepatitis. The combination of family history of liver cancer and hepatitis B/C serum markers is associated with an over 70-fold elevated HCC risk and poor prognosis. Only limited attention has been given to the role of primary genetic factors in HCC, but scattered anecdotal reports have identified familial aggregations of HCC. This article reviewed the literature on familial hepatocellular carcinoma and suggest that familial HCC may be a good model for studying preventive and therapeutic measures.
Highlights
Hepatocellular carcinoma (HCC) is one of the most commonly diagnosed cancer in the world with the incidence of 5.6% of total cancer cases [1,2]
Limited attention has been given to the role of primary genetic factors in HCC especially as familial clusters of HCC are mostly described in areas with endemic HBV infection (Table 1)
fibrolamellar variant of HCC (FHCC) mostly occurs in nonhepatitis B endemic areas, some cases have been reported in relatively endemic areas [35]
Summary
HCC is one of the most commonly diagnosed cancer in the world with the incidence of 5.6% of total cancer cases [1,2]. Hepatocellular carcinoma (HCC) usually affects patients aged 50–70 years but earlier onset (25–40 years) may occur in hepatitis B endemic areas [3]. Limited attention has been given to the role of primary genetic factors in HCC especially as familial clusters of HCC are mostly described in areas with endemic HBV infection (Table 1). Growing evidence suggests that a family history of liver cancer significantly increases HCC risk with an aggressive nature. A multifactorial inheritance including novel DICER I germline mutation and altered liver zonation could contribute to the risk, regardless of viral hepatitis infection [9]. A classical Mendelian inheritance of HCC is limited to rare cases including the rare monogenic diseases such as haemochromatosis, tyrosinaemia type 1 and alpha 1 antitrypsin deficiency [7,10]
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