PNPLA3 I148M (rs738409) genetic variant is associated with hepatocellular carcinoma in obese individuals.
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 PNPLA3 I148M 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.


CONCLUSIONS
The current study is the first prospective report showing the association of the PNPLA3 I148M genetic variant and hepatocellular carcinoma in severely obese individuals.
Department of Molecular and Clinical Medicine and Center for Cardiovascular and Metabolic Research, the Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Maria Antonella
MA
Burza
Carlo
C
Pirazzi
Cristina
C
Maglio
Kajsa
K
Sjöholm
Rosellina Margherita
RM
Mancina
Per-Arne
PA
Svensson
Peter
P
Jacobson
Martin
M
Adiels
Marco Giorgio
MG
Baroni
Jan
J
Borén
Stefano
S
Ginanni Corradini
Tiziana
T
Montalcini
Lars
L
Sjöström
Lena Mariana Susann
LM
Carlsson
Stefano
S
Romeo
D000328:Adult; D050110:Bariatric Surgery; D006528:Carcinoma, Hepatocellular / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D016014:Linear Models; D008049:Lipase / Q000235:genetics*; D008113:Liver Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009765:Obesity / Q000150:complications* / Q000601:surgery; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent
D005819:Genetic Markers; D008049:Lipase; D008565:Membrane Proteins; C533682:PNPLA3 protein, human; D000217:Acyltransferases; D054512:Phospholipases A2, Calcium-Independent