THYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO ESOPHAGEAL CANCER: A CASE-CONTROL STUDY
ABSTRACT BACKGROUND: The enzyme methylenetetrahydrofolate reductase is engaged in DNA synthesis through folate metabolism. Inhibiting the activity of this enzyme increases the susceptibility to mutations, and damage and aberrant DNA methylation, which alters the gene expression of tumor suppressors...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Colégio Brasileiro de Cirurgia Digestiva
2022-09-01
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| Series: | ABCD: Arquivos Brasileiros de Cirurgia Digestiva |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-67202022000100330&tlng=en |
| _version_ | 1828111941250318336 |
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| author | Evelise Pelegrinelli Zaidan Michele Tatiana Pereira Tomitão Marina Alessandra Pereira Marcia Saldanha Kubrusly Adriana Vaz Safatle-Ribeiro Flavio Roberto Takeda Ivan Cecconello Ulysses Ribeiro Junior |
| author_facet | Evelise Pelegrinelli Zaidan Michele Tatiana Pereira Tomitão Marina Alessandra Pereira Marcia Saldanha Kubrusly Adriana Vaz Safatle-Ribeiro Flavio Roberto Takeda Ivan Cecconello Ulysses Ribeiro Junior |
| author_sort | Evelise Pelegrinelli Zaidan |
| collection | DOAJ |
| description | ABSTRACT BACKGROUND: The enzyme methylenetetrahydrofolate reductase is engaged in DNA synthesis through folate metabolism. Inhibiting the activity of this enzyme increases the susceptibility to mutations, and damage and aberrant DNA methylation, which alters the gene expression of tumor suppressors and proto-oncogenes, potential risk factors for esophageal cancer. AIMS: This study aimed to investigate the association between methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and susceptibility to esophageal cancer, by assessing the distribution of genotypes and haplotypes between cases and controls, as well as to investigate the association of polymorphisms with clinical and epidemiological characteristics and survival. METHODS: A total of 109 esophageal cancer patients who underwent esophagectomy were evaluated, while 102 subjects constitute the control group. Genomic DNA was isolated from the peripheral blood buffy coat followed by amplification by polymerase chain reaction and real-time analysis. Logistic regression was used to assess associations between polymorphisms and the risk of developing esophageal cancer. RESULTS: There was no association for methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and haplotypes, with esophageal cancer susceptibility. Esophageal cancer patients carrying methylenetetrahydrofolate reductase 677TT polymorphism had higher risk of death from the disease. For polymorphic homozygote TT genotype, the risk of death significantly increased compared to wild-type genotype methylenetetrahydrofolate reductase 677CC (reference) cases (p=0.045; RR=2.22, 95%CI 1.02–4.83). CONCLUSIONS: There was no association between methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and esophageal cancer susceptibility risk. Polymorphic homozygote genotype methylenetetrahydrofolate reductase 677TT was associated with higher risk of death after surgical treatment for esophageal cancer. |
| first_indexed | 2024-04-11T11:42:46Z |
| format | Article |
| id | doaj.art-edc7b6df66a14a128d0b97e247e19654 |
| institution | Directory Open Access Journal |
| issn | 0102-6720 |
| language | English |
| last_indexed | 2024-04-11T11:42:46Z |
| publishDate | 2022-09-01 |
| publisher | Colégio Brasileiro de Cirurgia Digestiva |
| record_format | Article |
| series | ABCD: Arquivos Brasileiros de Cirurgia Digestiva |
| spelling | doaj.art-edc7b6df66a14a128d0b97e247e196542022-12-22T04:25:47ZengColégio Brasileiro de Cirurgia DigestivaABCD: Arquivos Brasileiros de Cirurgia Digestiva0102-67202022-09-013510.1590/0102-672020220002e1684THYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO ESOPHAGEAL CANCER: A CASE-CONTROL STUDYEvelise Pelegrinelli Zaidanhttps://orcid.org/0000-0002-9726-3274Michele Tatiana Pereira Tomitãohttps://orcid.org/0000-0003-2010-5646Marina Alessandra Pereirahttps://orcid.org/0000-0002-6865-0988Marcia Saldanha Kubruslyhttps://orcid.org/0000-0003-3258-5632Adriana Vaz Safatle-Ribeirohttps://orcid.org/0000-0001-7686-8859Flavio Roberto Takedahttps://orcid.org/0000-0001-7338-922XIvan Cecconellohttps://orcid.org/0000-0002-3535-4170Ulysses Ribeiro Juniorhttps://orcid.org/0000-0003-1711-7347ABSTRACT BACKGROUND: The enzyme methylenetetrahydrofolate reductase is engaged in DNA synthesis through folate metabolism. Inhibiting the activity of this enzyme increases the susceptibility to mutations, and damage and aberrant DNA methylation, which alters the gene expression of tumor suppressors and proto-oncogenes, potential risk factors for esophageal cancer. AIMS: This study aimed to investigate the association between methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and susceptibility to esophageal cancer, by assessing the distribution of genotypes and haplotypes between cases and controls, as well as to investigate the association of polymorphisms with clinical and epidemiological characteristics and survival. METHODS: A total of 109 esophageal cancer patients who underwent esophagectomy were evaluated, while 102 subjects constitute the control group. Genomic DNA was isolated from the peripheral blood buffy coat followed by amplification by polymerase chain reaction and real-time analysis. Logistic regression was used to assess associations between polymorphisms and the risk of developing esophageal cancer. RESULTS: There was no association for methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and haplotypes, with esophageal cancer susceptibility. Esophageal cancer patients carrying methylenetetrahydrofolate reductase 677TT polymorphism had higher risk of death from the disease. For polymorphic homozygote TT genotype, the risk of death significantly increased compared to wild-type genotype methylenetetrahydrofolate reductase 677CC (reference) cases (p=0.045; RR=2.22, 95%CI 1.02–4.83). CONCLUSIONS: There was no association between methylenetetrahydrofolate reductase 677C>T and methylenetetrahydrofolate reductase 1298A>C polymorphisms and esophageal cancer susceptibility risk. Polymorphic homozygote genotype methylenetetrahydrofolate reductase 677TT was associated with higher risk of death after surgical treatment for esophageal cancer.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-67202022000100330&tlng=enEsophageal NeoplasmsAdenocarcinomaCarcinoma, Squamous CellPolymorphism, GeneticMethylenetetrahydrofolate Reductase (NADPH2) |
| spellingShingle | Evelise Pelegrinelli Zaidan Michele Tatiana Pereira Tomitão Marina Alessandra Pereira Marcia Saldanha Kubrusly Adriana Vaz Safatle-Ribeiro Flavio Roberto Takeda Ivan Cecconello Ulysses Ribeiro Junior THYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO ESOPHAGEAL CANCER: A CASE-CONTROL STUDY ABCD: Arquivos Brasileiros de Cirurgia Digestiva Esophageal Neoplasms Adenocarcinoma Carcinoma, Squamous Cell Polymorphism, Genetic Methylenetetrahydrofolate Reductase (NADPH2) |
| title | THYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO ESOPHAGEAL CANCER: A CASE-CONTROL STUDY |
| title_full | THYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO ESOPHAGEAL CANCER: A CASE-CONTROL STUDY |
| title_fullStr | THYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO ESOPHAGEAL CANCER: A CASE-CONTROL STUDY |
| title_full_unstemmed | THYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO ESOPHAGEAL CANCER: A CASE-CONTROL STUDY |
| title_short | THYLENETETRAHYDROFOLATE REDUCTASE GENE POLYMORPHISMS AND SUSCEPTIBILITY TO ESOPHAGEAL CANCER: A CASE-CONTROL STUDY |
| title_sort | thylenetetrahydrofolate reductase gene polymorphisms and susceptibility to esophageal cancer a case control study |
| topic | Esophageal Neoplasms Adenocarcinoma Carcinoma, Squamous Cell Polymorphism, Genetic Methylenetetrahydrofolate Reductase (NADPH2) |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0102-67202022000100330&tlng=en |
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