Titre
Association between the PNPLA3 (rs738409 C>G) variant and hepatocellular carcinoma: Evidence from a meta-analysis of individual participant data.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Trépo, E.
Auteure/Auteur
Nahon, P.
Auteure/Auteur
Bontempi, G.
Auteure/Auteur
Valenti, L.
Auteure/Auteur
Falleti, E.
Auteure/Auteur
Nischalke, H.D.
Auteure/Auteur
Hamza, S.
Auteure/Auteur
Corradini, S.G.
Auteure/Auteur
Burza, M.A.
Auteure/Auteur
Guyot, E.
Auteure/Auteur
Donati, B.
Auteure/Auteur
Spengler, U.
Auteure/Auteur
Hillon, P.
Auteure/Auteur
Toniutto, P.
Auteure/Auteur
Henrion, J.
Auteure/Auteur
Franchimont, D.
Auteure/Auteur
Devière, J.
Auteure/Auteur
Mathurin, P.
Auteure/Auteur
Moreno, C.
Auteure/Auteur
Romeo, S.
Auteure/Auteur
Deltenre, P.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1527-3350
Statut éditorial
Publié
Date de publication
2014
Volume
59
Numéro
6
Première page
2170
Dernière page/numéro d’article
2177
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
The incidence of hepatocellular carcinoma (HCC) is increasing in Western countries. Although several clinical factors have been identified, many individuals never develop HCC, suggesting a genetic susceptibility. However, to date, only a few single-nucleotide polymorphisms have been reproducibly shown to be linked to HCC onset. A variant (rs738409 C>G, encoding for p.I148M) 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 HCC cases in chronic hepatitis C (CHC) and alcoholic liver disease (ALD). However, a significant association with HCC related to CHC has not been consistently observed, and the strength of the association between rs738409 and HCC remains unclear. We 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 ALD and CHC. We found that rs738409 was strongly associated with overall HCC (odds ratio [OR] per G allele, additive model=1.77; 95% confidence interval [CI]: 1.42-2.19; P=2.78 × 10(-7) ). This association was more pronounced in ALD (OR=2.20; 95% CI: 1.80-2.67; P=4.71 × 10(-15) ) than in CHC patients (OR=1.55; 95% CI: 1.03-2.34; P=3.52 × 10(-2) ). After adjustment for age, sex, and body mass index, the variant remained strongly associated with HCC. Conclusion: 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 HCC development.
PID Serval
serval:BIB_E43635F45B25
PMID
Open Access
Oui
Date de création
2014-07-18T17:01:22.554Z
Date de création dans IRIS
2025-05-21T05:12:47Z