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- Title
PNPLA3 I148M Polymorphism, Clinical Presentation, and Survival in Patients with Hepatocellular Carcinoma.
- Authors
Valenti, Luca; Motta, Benedetta Maria; Soardo, Giorgio; Iavarone, Massimo; Donati, Benedetta; Sangiovanni, Angelo; Carnelutti, Alessia; Dongiovanni, Paola; Rametta, Raffaela; Bertelli, Cristina; Facchetti, Floriana; Colombo, Massimo; Fargion, Silvia; Fracanzani, Anna Ludovica
- Abstract
Background & Aims: Aim of this study was to evaluate whether the PNPLA3 I148M polymorphism, previously associated with hepatocellular carcinoma (HCC) risk, influences the clinical presentation of HCC and survival. Methods: we considered 460 consecutive HCC patients referred to tertiary care centers in Northern Italy, 353 with follow-up data. Results: Homozygosity for PNPLA3 148M at risk allele was enriched in HCC patients with alcoholic liver disease or nonalcoholic fatty liver disease (ALD&NAFLD: relative risk 5.9, 95% c.i. 3.5–9.9; other liver diseases: relative risk 1.9, 95% c.i. 1.1–3.4). In ALD&NAFLD patients, the PNPLA3 148M allele was associated with younger age, shorter history of cirrhosis, less advanced (Child A) cirrhosis at HCC diagnosis, and lower HCC differentiation grade (p<0.05). Homozygosity for PNPLA3 148M was associated with reduced survival in the overall series (p = 0.009), and with a higher number of HCC lesions at presentation (p = 0.007) and reduced survival in ALD&NAFLD patients (p = 0.003; median survival 30, 95% c.i. 20–39 vs. 45, 95% c.i. 38–52 months), but not in those with HCC related to other etiologies (p = 0.86; 48, 95% c.i. 32–64 vs. 55, 95% c.i. 43–67 months). At multivariate Cox regression analysis, homozygosity for PNPLA3 148M was the only negative predictor of survival in ALD&NAFLD patients (HR of death 1.57, 95% c.i. 1.12–2.78). Conclusions: PNPLA3 148M is over-represented in ALD&NAFLD HCC patients, and is associated with occurrence at a less advanced stage of liver disease in ALD&NAFLD. In ALD&NAFLD, PNPLA3 148M is associated with more diffuse HCC at presentation, and with reduced survival.
- Subjects
LIVER cancer; GENETIC polymorphisms; PHOSPHOLIPASES; HOMOZYGOSITY; ALCOHOLIC liver diseases; TERTIARY care; FOLLOW-up studies (Medicine); GENETICS
- Publication
PLoS ONE, 2013, Vol 8, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0075982