Pancreatic injury, genetic variation of PNPLA3, and risk of pancreatic cancer.

Abstract

141 Background: Similar to primary liver cancer, obesity, diabetes mellitus and hepatitis B virus infection have been associated with increased risk of pancreatic cancer (PC) development. A genome-wide association study has reported that a polymorphic variant of the patatin-like phospholipase domain containing 3 (PNPLA3) gene was associated with a higher susceptibility to fatty liver and liver cancer. The relationship between this variation and PC has not been previously examined. We investigated the correlation in the degree of organ damage between the liver and the pancreas in patients with PC. In addition, we examined the effect of PNPLA3genetic variation (rs738409: C>G) on PC development. Methods: Using resources of our case-control study in MD Anderson Cancer Center, we analyzed 544 pathologically confirmed PC patients and 498 healthy controls. Cases and controls were frequency matched by age, gender, and race. Multivariate logistic regression analysis was performed to adjust for the confounding factors. Medical records of PC patients were reviewed for pancreatic and liver fatty changes. Results: We found that 18.8% of PC patients had evidence of pancreatic steatosis, fibrosis, or pancreatitis. Fatty liver was observed in 14.5% of PC patients which was frequently detected in patients with pancreatitis (p=0.002). A significant correlation between pancreatitis and cirrhosis was observed in PC patients with a prior history of obesity but not in patients without a history of obesity (p=0.001). On the other hand, we observed no significant association between PNPLA3 genotype and risk of PC. The adjusted odds ratio (OR) was 1.4 (95% confidence interval [CI], 0.7-2.7) for the homozygous variant GG genotype compared with the CC/CG genotypes. Conclusions: We concluded that despite the similarities between the liver and the pancreas, genetic susceptibility to fatty infiltration and its effect on cancer development may differ between the two organs. Evaluation and assessment of nonalcoholic fatty pancreatic disease (NAFPD) in PC patients and genetic susceptibility of NAFPD may be warranted in future research.