The impact of patatin-like phospholipase domain-containing protein 3 polymorphism on hepatocellular carcinoma prognosis

• Published in: Journal of gastroenterology Vol. 48; no. 3; pp. 405 - 412
• Main Authors: Takeuchi, Yasuto, Ikeda, Fusao, Moritou, Yuki, Hagihara, Hiroaki, Yasunaka, Tetsuya, Kuwaki, Kenji, Miyake, Yasuhiro, Ohnishi, Hideki, Nakamura, Shinichiro, Shiraha, Hidenori, Takaki, Akinobu, Iwasaki, Yoshiaki, Nouso, Kazuhiro, Yamamoto, Kazuhide
• Format: Journal Article
• Language: English
• Published: Japan Springer Japan 01.03.2013; Springer; Springer Nature B.V
• Subjects: Abdominal Surgery; Adult; Aged; Aged, 80 and over; Aspartate; Biliary Tract; Body Mass Index; Carcinoma, Hepatocellular - diagnosis; Carcinoma, Hepatocellular - genetics; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - virology; Colorectal Surgery; Development and progression; Female; Follow-Up Studies; Gastroenterology; Genetic aspects; Genotype; Health aspects; Hepatitis B; Hepatitis B, Chronic - complications; Hepatitis C virus; Hepatitis C, Chronic - complications; Hepatitis E - complications; Hepatology; Hepatoma; Humans; Kaplan-Meier Estimate; Lipase - genetics; Liver; Liver cirrhosis; Liver Neoplasms - diagnosis; Liver Neoplasms - genetics; Liver Neoplasms - pathology; Liver Neoplasms - virology; Male; Medical research; Medicine; Medicine & Public Health; Medicine, Experimental; Membrane Proteins - genetics; Middle Aged; Neoplasm Staging; Original Article—Liver; Pancreas; Phospholipases; Polymorphism, Single Nucleotide; Prognosis; Single nucleotide polymorphisms; Surgical Oncology; Hepatocellular carcinoma; Survival; PNPLA3 SNP
• ISSN: 0944-1174; 1435-5922
• DOI: 10.1007/s00535-012-0647-3

Background The single nucleotide polymorphism (SNP) rs738409 in patatin-like phospholipase domain-containing protein 3 (PNPLA3) is associated with hepatic fat accumulation and disease progression in patients with non-alcoholic fatty liver disease and alcoholic liver disease (ALD). This study was conducted to determine whether PNPLA3 rs738409 SNPs affect development and prognosis of hepatocellular carcinoma (HCC) in patients with various liver diseases. Methods We enrolled 638 consecutive Japanese patients newly diagnosed with HCC between 2001 and 2010: 72 patients with hepatitis B virus (HBV), 462 with hepatitis C virus (HCV), and 104 with non-B non-C (NBNC). Results NBNC patients exhibited large tumors of advanced TNM stages at HCC diagnosis, and had significantly poorer prognosis than HBV or HCV patients ( P  < 0.001 and <0.001, respectively; log-rank test). The G/G genotype of PNPLA3 rs738409 SNP had significantly higher distribution in NBNC patients ( P  < 0.001) and was significantly associated with higher body mass index (BMI) and an increased aspartate aminotransferase to platelet ratio index. No significant differences were observed in survival with differences in PNPLA3 SNP genotypes among the patients, although ALD patients with the G/G genotype of PNPLA3 SNP and low BMI had significantly poorer survival than those with high BMI ( P  = 0.028). Conclusions The G/G genotype of PNPLA3 rs738409 SNP was more frequently distributed, and associated with BMI and fibrosis among NBNC-HCC patients but not among HBV or HCV patients. These genotypes might affect HCC prognosis in ALD patients, but not in HBV, HCV, or NAFLD patients.