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Independent and additive effects of PNPLA3 and TM6SF2 polymorphisms on the development of non-B, non-C hepatocellular carcinoma

Authors
  • Raksayot, Maneerat1
  • Chuaypen, Natthaya1
  • Khlaiphuengsin, Apichaya1
  • Pinjaroen, Nutcha2
  • Treeprasertsuk, Sombat3
  • Poovorawan, Yong4
  • Tanaka, Yasuhito5
  • Tangkijvanich, Pisit1
  • 1 Chulalongkorn University, Center of Excellence in Hepatitis and Liver Cancer, Department of Biochemistry, Faculty of Medicine, Bangkok, 10330, Thailand , Bangkok (Thailand)
  • 2 Chulalongkorn University, Department of Radiology, Faculty of Medicine, Bangkok, 10330, Thailand , Bangkok (Thailand)
  • 3 Chulalongkorn University, Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Bangkok, 10330, Thailand , Bangkok (Thailand)
  • 4 Chulalongkorn University, Center of Excellence in Clinical Virology, Department of Pediatrics, Faculty of Medicine, Bangkok, 10330, Thailand , Bangkok (Thailand)
  • 5 Nagoya City University Graduate School of Medical Sciences, Department of Virology and Liver Unit, Nagoya, Japan , Nagoya (Japan)
Type
Published Article
Journal
Journal of Gastroenterology
Publisher
Springer Japan
Publication Date
Nov 30, 2018
Volume
54
Issue
5
Pages
427–436
Identifiers
DOI: 10.1007/s00535-018-01533-x
Source
Springer Nature
Keywords
License
Yellow

Abstract

BackgroundThis study was aimed at evaluating the association between single nucleotide polymorphisms (SNPs) in the PNPLA3, NCAN, TM6SF2 and MBOAT7 and hepatocellular carcinoma (HCC) development in Thai patients according to underlying etiologies of liver disease.MethodsThese SNPs were determined by allelic discrimination in blood samples of 105 healthy controls and 530 patients with HCC [270 with hepatitis B virus (HBV-HCC), 131 with hepatitis C virus (HCV-HCC), and 129 with non-B, non-C HCC (NBNC-HCC) matched for age and gender].ResultsG allele of PNPLA3 rs738409 variant was significantly higher in NBNC-HCC (49%) compared to healthy controls (32%), HBV-HCC (32%) and HCV-HCC (31%) (P < 0.001). T allele of TM6SF2 rs58542926 was more prevalent in NBNC-HCC (24%) than in healthy controls (8%), HBV-HCC (10%) and HCV-HCC (12%) (P < 0.001). The distribution of NCAN (rs2228603) and MBOAT7 (rs641738) was not different between groups. In multivariate logistic regression analysis, PNPLA3 rs738409 (OR 2.06, 95% CI 1.24–3.43; P = 0.005) and TM6SF2 rs58542926 (OR 2.22, 95% CI 1.34–3.65; P = 0.002) were independently associated with NBNC-HCC compared to viral-related HCC (VR-HCC). The proportion of patients with NBNC-HCC increased significantly along with the increase of the number of risk alleles. There was no association between these SNPs and overall survival in patients with HCC.ConclusionsThese data showed that PNPLA3 and TM6SF2 polymorphisms were independently linked to NBNC-HCC but not HBV- or HCV-HCC in Thai populations. In addition, the risk genotypes might interact with each other through tumor development in patients with NBNC-HCC.

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