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.
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The authors thank the patients of the Hospital de Clínicas de Porto Alegre for their collaboration on this study.
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This work was supported by the Universidade Luterana do Brasil, Hospital de Clínicas de Porto Alegre, and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES - Finance Code 001).
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Conceived and designed the experiments: CGM MRAS DS. Performed the experiments: CGM JTB DCS. Analyzed the data: CGM MRAS RTM DS. Contributed reagents/analysis tools: VRL. Wrote the paper: CGM RTM DS.
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Marangon, C.G., de Bitencorte, J.T., Michita, R.T. et al. Association between MICA rs2596542 Polymorphism with the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients. Pathol. Oncol. Res. 26, 1519–1525 (2020). https://doi.org/10.1007/s12253-019-00738-6
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DOI: https://doi.org/10.1007/s12253-019-00738-6