ABSTRACT
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.
RESUMO RACIONAL: A enzima metilenotetrahidrofolato redutase está envolvida na síntese de DNA através do metabolismo do folato. A inibição da sua atividade aumenta a suscetibilidade a mutações, danos e metilação aberrante do DNA, o que altera a expressão gênica de supressores tumorais e proto-oncogenes, potenciais fatores de risco para câncer de esôfago. OBJETIVOS: Investigar a associação entre os polimorfismos metilenotetrahidrofolato redutase 677C>T e metilenotetrahidrofolato redutase 1298A>C e a suscetibilidade ao câncer de esôfago, avaliando a distribuição de genótipos e haplótipos entre casos e controles, bem como investigar a associação de polimorfismos com características clínicas, epidemiológicas e sobrevida. MÉTODOS: Avaliaram-se 109 pacientes com câncer de esôfago submetidos à esofagectomia, enquanto 102 indivíduos constituaram o grupo controle. O DNA genômico do sangue periférico foi isolado e submetido à amplificação por reação em cadeia da polimerase em tempo real. A associação entre os polimorfismos e o risco de desenvolver câncer de esôfago foi avaliada por regressão logística. RESULTADOS: Não houve associação dos polimorfismos e haplótipos metilenotetrahidrofolato redutase 677C>T e metilenotetrahidrofolato redutase 1298A>C com a suscetibilidade ao câncer de esôfago. Pacientes com câncer de esôfago portadores do polimorfismo metilenotetrahidrofolato redutase 677TT apresentaram maior risco de morte pela doença. Para o genótipo TT homozigoto polimórfico, o risco de morte aumentou significativamente em comparação com os casos do genótipo selvagem metilenotetrahidrofolato redutase 677CC (referência) (p=0,045; RR=2,22, IC95% 1,02-4,83). CONCLUSÕES: Não houve associação entre os polimorfismos metilenotetrahidrofolato redutase 677C>T e metilenotetrahidrofolato redutase 1298A>C e o risco de suscetibilidade ao câncer de esôfago. O genótipo homozigoto polimórfico metilenotetrahidrofolato redutase 677TT associou-se a um maior risco de óbito após tratamento cirúrgico para câncer de esôfago.
ABSTRACT
OBJECTIVES: Surgery remains the cornerstone treatment modality for gastric cancer, the fifth most common type of tumor in Brazil. The aim of this study was to analyze the surgical treatment outcomes of patients with gastric cancer who were referred to a high-volume university hospital. METHODS: We reviewed all consecutive patients who underwent any surgical procedure due to gastric cancer from a prospectively collected database. Clinicopathological characteristics, surgical and survival outcomes were evaluated, with emphasis on patients treated with curative intent. RESULTS: From 2008 to 2017, 934 patients with gastric tumors underwent surgical procedures in our center. Gastric adenocarcinoma accounted for the majority of cases. Of the 875 patients with gastric adenocarcinoma, resection with curative intent was performed in 63.5%, and palliative treatment was performed in 22.4%. The postoperative surgical mortality rate for resected cases was 5.3% and was related to D1 lymphadenectomy and the presence of comorbidities. Analysis of patients treated with curative intent showed that resection extent, pT category, pN category and final pTNM stage were related to disease-free survival (DFS) and overall survival (OS). The DFS rates for D1 and D2 lymphadenectomy were similar, but D2 lymphadenectomy significantly improved the OS rate. Additionally, clinical factors and the presence of comorbidities had influence on the OS. CONCLUSIONS: TNM stage and the type of lymphadenectomy were independent factors related to prognosis. Early diagnosis should be sought to offer the optimal surgical approach in patients with less-advanced disease.