Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)

OBJECTIVE: The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellula...

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Main Authors: Sylene C.R. Carvalho, Luydson R.S. Vasconcelos, Leonardo da Fonseca, Rodrigo F. Carmo, Michele T. Tomitão, Dayse C.B.L. Aroucha, Leila M.M.B. Pereira, José Tadeu Stefano, Ulysses Ribeiro-Júnior, Claudia P. Oliveira, Flair J. Carrilho
Format: Article
Language:English
Published: Elsevier España 2021-10-01
Series:Clinics
Subjects:
Online Access:http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322021000100313&tlng=en
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author Sylene C.R. Carvalho
Luydson R.S. Vasconcelos
Leonardo da Fonseca
Rodrigo F. Carmo
Michele T. Tomitão
Dayse C.B.L. Aroucha
Leila M.M.B. Pereira
José Tadeu Stefano
Ulysses Ribeiro-Júnior
Claudia P. Oliveira
Flair J. Carrilho
author_facet Sylene C.R. Carvalho
Luydson R.S. Vasconcelos
Leonardo da Fonseca
Rodrigo F. Carmo
Michele T. Tomitão
Dayse C.B.L. Aroucha
Leila M.M.B. Pereira
José Tadeu Stefano
Ulysses Ribeiro-Júnior
Claudia P. Oliveira
Flair J. Carrilho
author_sort Sylene C.R. Carvalho
collection DOAJ
description OBJECTIVE: The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC. METHODS: A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated. RESULTS: The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0.04 OR 1.835 CI (1.022-3.297)]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 CI (1.38-16.67)]. CONCLUSION: Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.
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spelling doaj.art-a584ef361cb04c3aa9ea5b472c9b557c2022-12-22T00:21:19ZengElsevier EspañaClinics1980-53222021-10-017610.6061/clinics/2021/e2881Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)Sylene C.R. Carvalhohttps://orcid.org/0000-0003-0922-701XLuydson R.S. Vasconceloshttps://orcid.org/0000-0002-1625-3358Leonardo da Fonsecahttps://orcid.org/0000-0002-0216-3618Rodrigo F. Carmohttps://orcid.org/0000-0001-9601-6995Michele T. Tomitãohttps://orcid.org/0000-0003-2010-5646Dayse C.B.L. Arouchahttps://orcid.org/0000-0001-9184-6885Leila M.M.B. Pereirahttps://orcid.org/0000-0002-0616-8811José Tadeu Stefanohttps://orcid.org/0000-0002-0218-1920Ulysses Ribeiro-Júniorhttps://orcid.org/0000-0003-1711-7347Claudia P. Oliveirahttps://orcid.org/0000-0002-2848-417XFlair J. Carrilhohttps://orcid.org/0000-0002-7682-3105OBJECTIVE: The folate pathway is involved in hepatic carcinogenesis and angiogenesis. Polymorphisms in genes related to such processes, including methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF)] may play an important role in the development of hepatocellular carcinoma (HCC). The objective of this study was to evaluate MTHFR and VEGF polymorphisms in Brazilian patients with hepatitis C virus (HCV)-related HCC. METHODS: A total of 119 patients diagnosed with confirmed HCC and HCV were included in the study. SNP genotyping assays were performed using real-time PCR. VEGFA (rs2010963, rs3025039, and rs833061) and MTHFRC677T (rs1801133, rs1801131) polymorphisms were evaluated. RESULTS: The C alleles of MTHFR (rs1801131) and VEGF (rs2010963) were associated with protection against the development of multinodular HCC, while the T allele of MTHFR (rs1801133) was associated with a higher risk of multinodular presentation [p=0.04 OR 1.835 CI (1.022-3.297)]. Multivariate analysis revealed that the GG/GC genotypes of VEGF rs2010963 were independently associated with multinodular tumors at diagnosis (p=0.013; OR 4.78 CI (1.38-16.67)]. CONCLUSION: Our results suggest that these polymorphisms may increase the risk of rapid tumor progression in patients with HCV infection. This subgroup of patients with HCC and who present polymorphism is more likely to be diagnosed with multinodular disease and not be amenable to receiving curative treatments. These data must be validated in larger cohorts, and the screening intervals can be customized based on genetic history.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322021000100313&tlng=enPolymorphismsMethylene Tetrahydrofolate ReductaseVascular Endothelial Growth FactorHepatocellular CarcinomaHepatitis C
spellingShingle Sylene C.R. Carvalho
Luydson R.S. Vasconcelos
Leonardo da Fonseca
Rodrigo F. Carmo
Michele T. Tomitão
Dayse C.B.L. Aroucha
Leila M.M.B. Pereira
José Tadeu Stefano
Ulysses Ribeiro-Júnior
Claudia P. Oliveira
Flair J. Carrilho
Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)
Clinics
Polymorphisms
Methylene Tetrahydrofolate Reductase
Vascular Endothelial Growth Factor
Hepatocellular Carcinoma
Hepatitis C
title Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)
title_full Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)
title_fullStr Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)
title_full_unstemmed Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)
title_short Methylene tetrahydrofolate reductase (MTHFR) and vascular endothelial growth factor (VEGF) polymorphisms in Brazilian patients with Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC)
title_sort methylene tetrahydrofolate reductase mthfr and vascular endothelial growth factor vegf polymorphisms in brazilian patients with hepatitis c virus hcv related hepatocellular carcinoma hcc
topic Polymorphisms
Methylene Tetrahydrofolate Reductase
Vascular Endothelial Growth Factor
Hepatocellular Carcinoma
Hepatitis C
url http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1807-59322021000100313&tlng=en
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