Association between MICA rs2596542 Polymorphism with the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients

Pathol Oncol Res. 2020 Jul;26(3):1519-1525. doi: 10.1007/s12253-019-00738-6. Epub 2019 Aug 31.

Abstract

In this study we investigated the impact of rs2596542A/G single nucleotide polymorphism (SNP) in the major histocompatibility complex class I chain-related sequence A (MICA) gene on HCV-induced hepatocellular carcinoma (HCC) susceptibility in a Brazilian population. In total, 252 HCV-infected patients (98 with HCV-induced HCC and 154 non-malignant HCV-induced liver cirrhosis) were enrolled and 98 healthy control subjects (negative anti-HCV). The MICA rs2596542 SNP genotypes were determined by real-time PCR assay. No differences in MICA genotype frequencies between HCV-induced cirrhosis patients and controls were observed. However, genotype frequencies of rs2596542A/G SNP were statistically different between HCV-induced HCC patients and controls (p = 0.048), and also between HCC and HCV-induced cirrhosis patients (p = 0.039). The highest frequency of the rs2596542AA genotype was observed in HCC patients (31.6%) when compared with HCV-induced cirrhosis patients (18.8%) and healthy controls (19.4%). Also, rs2596542AA genotype carriers have an increased risk for HCC when compared to HCV-induced cirrhosis status [odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.06-3.74, p = 0.020)] and healthy individuals (OR = 1.92, 95% CI = 1.00-3.70, p = 0.049). Taken together our study suggest that MICA rs2596542 SNP impacts HCV-induced HCC susceptibility suggesting that genetic variants in MICA are of clinical relevance to hepatocarcinogenesis by impacting host immune response in chronic HCV infection.

Keywords: HCV; Hepatocellular carcinoma; Liver cirrhosis; MICA gene; rs2596542, HCC.

MeSH terms

  • Aged
  • Brazil
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology*
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Hepatitis C, Chronic / complications*
  • Histocompatibility Antigens Class I / genetics*
  • Humans
  • Liver Neoplasms / etiology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide

Substances

  • Histocompatibility Antigens Class I
  • MHC class I-related chain A