PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals
Journal article, 2012

Background: Obesity is a risk factor for cancer, including hepatocellular carcinoma. Patatin-like phospholipase domain-containing 3 (PNPLA3) I148M (rs738409) genetic variant has been associated with hepatocellular carcinoma (HCC) in individuals with chronic alcohol abuse or hepatic viral infection. In the present study we examined the association between the PNPLA3I148M genetic variant and hepatocellular carcinoma in obese individuals from the Swedish Obese Subjects cohort (n=4047). Methods: We performed a matched, prospective, controlled, interventional trial, investigating the effect of bariatric surgery (surgery group) compared to conventional treatment (control group) for obesity. Results: A total of 9 events were observed in the 15-year median follow up (5 in the control group and 4 in the surgery group). A significantly higher incidence of hepatocellular carcinoma in PNPLA3 148M allele carriers was found in obese individuals in the control group (log-rank P-value=0.001), but not in the surgery group (log-rank P-value=0.783). Consistently, an increased risk (for each PNPLA3 148M allele, hazard ratio: 5.9; 95% confidence interval 1.5-23.8; P-value=0.013) of developing hepatocellular carcinoma was observed only in the control group. Conclusion: The current study is the first prospective report showing the association of the PNPLA3I148M genetic variant and hepatocellular carcinoma in severely obese individuals.



histological severity


Patatin-like phospholipase domain-containing 3

fatty liver-disease

bariatric surgery

Swedish obese subjects study





Liver cancer



Maria A Burza

University of Gothenburg

Carlo Pirazzi

University of Gothenburg

Cristina Maglio

University of Gothenburg

Kajsa Sjöholm

University of Gothenburg

Rosellina Margherita Mancina

University of Gothenburg

Per-Arne Svensson

University of Gothenburg

Peter Jacobson

University of Gothenburg

Martin Adiels

University of Gothenburg

M. G. Baroni

Jan Borén

University of Gothenburg

S. G. Corradini

T. Montalcini

Lars Sjöström

University of Gothenburg

Lena M S Carlsson

University of Gothenburg

Stefano Romeo

University of Gothenburg

Digestive and Liver Disease

1590-8658 (ISSN)

Vol. 44 12 1037-1041

Subject Categories

Clinical Medicine



More information