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News

Association between the PNPLA3 variant and hepatocellular carcinoma

The latest issue of Hepatology examines the association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma.

News image

The incidence of hepatocellular carcinoma is increasing in Western countries.

Although several clinical factors have been identified, many individuals never develop hepatocellular carcinoma, suggesting a genetic susceptibility.

However, to date, only a few single-nucleotide polymorphisms have been reproducibly shown to be linked to hepatocellular carcinoma onset.

A variant in the PNPLA3 gene is associated with liver damage in chronic liver diseases.

Interestingly, several studies have reported that the minor rs738409[G] allele is more represented in hepatocellular carcinoma cases in chronic hepatitis C and alcoholic liver disease.

rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis 
Hepatology

However, a significant association with hepatocellular carcinoma related to chronic hepatitis C has not been consistently observed, and the strength of the association between rs738409 and HCC remains unclear.

Dr Pierre Deltenre and colleagues from Belgium performed a meta-analysis of individual participant data including 2,503 European patients with cirrhosis to assess the association between rs738409 and HCC, particularly in alcoholic liver disease and chronic hepatitis C.

The research team found that rs738409 was strongly associated with overall hepatocellular carcinoma.

The team found that this association was more pronounced in alcoholic liver disease than in chronic hepatitis C patients.

After adjustment for age, sex, and body mass index, the variant remained strongly associated with hepatocellular carcinoma.

Dr Deltenre's team concludes, "Overall, these results suggest that rs738409 exerts a marked influence on hepatocarcinogenesis in patients with cirrhosis of European descent and provide a strong argument for performing further mechanistic studies to better understand the role of PNPLA3 in hepatocellular carcinoma development."

Hepatology 2014: 59(6): 21702177
18 June 2014

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