Polymorphisms in methylenetetrahydrofolate reductase and cystathionine beta-synthase in oral cancer – a case–control study in southeastern Brazilians

Andressa Barbosa,Marcelo Dos Santos,José Roberto Vasconcelos De Podestá,Sônia Alves Gouvêa,Sandra Ventorin Von Zeidler,Iúri Drumond Louro,Melissa De Freitas Cordeiro-Silva

doi:10.1016/j.bjorl.2015.10.012

Abstract

IntroductionOral squamous cell carcinoma (OSCC) is a serious public health problem, due to its high mortality rate and worldwide rising incidence. OSCC susceptibility is mediated by interactions between genetic and environmental factors. Studies suggest that genetic variants encoding enzymes involved in folate metabolism may modulate OSCC risk by altering DNA synthesis/repair and methylation process. ObjectiveThe goals of this study were to evaluate the association of three genotypic polymorphism (MTHFR C677T, MTHFR A1298C and CBS 844ins68) and oral cancer risk in southeastern Brazilians and evaluate the interactions between polymorphisms and clinical histopathological parameters. MethodsThis case–control study included 101 cases and 102 controls in the state of Espírito Santo, Brazil. MTHFR genotyping was done by PCR-RFLP (polymerase chain reaction – restriction fragment length polymorphism) and CBS genotyping by PCR (polymerase chain reaction) analysis. ResultsMTHFR C677T polymorphism was associated with lymph node involvement. Genotype CT+TT acted as a protective factor. MTHFR A1298C AC+CC genotype was associated with tumor differentiation, and possibly with a better prognosis. In risk analysis, no correlation was observed between genotypes and OSCC. ConclusionWe concluded that MTHFR C677T, MTHFR A1298C and CBS 844ins68 polymorphisms were not associated with OSCC risk in southeastern Brazilians; however, we suggest a prognosis effect associated with MTHFR C677T and A1298C polymorphisms in OSCC.

Highlights

Oral squamous cell carcinoma (OSCC) is a serious public health problem, due to its high mortality rate and worldwide rising incidence
Studies have shown a relationship between polymorphisms of genes involved in folate metabolism and OSCC risk due to their influence on methylation, synthesis and DNA repair.3---7
This study aimed to investigate the frequency and association of MTHFR and cystathionine beta synthase (CBS) polymorphisms in oral cancer susceptibility in the population of the state of Espírito Santo, Brazil and its potential impact on the prognostic outcome. In this case---control study, blood samples were collected from 101 patients with conclusive histopathological diagnostic of oral squamous cell carcinoma obtained from the Head and Neck Division of the Hospital Santa Rita de Cássia, Brazil

Summary

Introduction

Oral squamous cell carcinoma (OSCC) is a serious public health problem, due to its high mortality rate and worldwide rising incidence. Studies suggest that genetic variants encoding enzymes involved in folate metabolism may modulate OSCC risk by altering DNA synthesis/repair and methylation process. Objective: The goals of this study were to evaluate the association of three genotypic polymorphism (MTHFR C677T, MTHFR A1298C and CBS 844ins68) and oral cancer risk in southeastern Brazilians and evaluate the interactions between polymorphisms and clinical histopathological parameters. Studies have shown a relationship between polymorphisms of genes involved in folate metabolism and OSCC risk due to their influence on methylation, synthesis and DNA repair.3---7. Polymorphisms C677T and A1298C in the MTHFR gene may be associated with oral cancer susceptibility due to changes in catalytic activity. Reduced MTHFR enzyme activity increases the availability of folate for the production of thymidylate and purine for DNA synthesis and repair.[12]

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