Avaliação de polimorfismos nos genes MTHFR, MTR, RFC1 e CßS envolvidos no metabolismo do folato em pacientes com câncer de tireoide

Abstract

Introduction: Thyroid cancer is the most common malignancy of the endocrine system and has been presenting continuous increase in the last years. Studies suggest that folate deficiency in the body decrease DNA repair, resulting in malignant cells changes that alter expression of genes, and may induce several kinds of cancer development. Polymorphisms in genes involved in folate pathway have been investigated as risk factors for susceptibility to cancer, among them MTHFR, MTR, RFC1 and CßS. Objectives: To investigate association of polymorphisms in the MTHFR (C677T), MTR (A2756G), RFC1 (A80G) and CßS (844ins68) genes in risk thyroid cancer in a case-control study; to evaluate the association of polymorphisms with gender, age, alcohol and tobacco consumption, body-mass index in thyroid cancer development; and to evaluated the association between polymorphisms and clinical-histopathological parameters. Methods: This study included 462 individuals (151 patients with thyroid cancer and 311 controls). The peripheral blood was collected and genomic DNA was extracted. The MTHFR (C677T), MTR (A2756G) and RFC1 (A80G) were evaluated by PCR-RFLP and CßS (844ins68) by conventional PCR without enzymatic digestion. For statistical analysis chi-square and multiple logistic regression were used. Results: The results showed that MTHFR C677T (OR=2.87, 95% CI=1.50-5.48, p< 0.01, codominant model), (OR=1.76, 95% CI=1.18-2.64, p< 0.01, dominant model), (OR=2.37, 95% CI=1.28-4.39, p< 0.01, recessive model) and RFC1 A80G (OR: 1.55; 95% CI: 1.02-2.38; p=0.04, recessive model) were associated with thyroid cancer. The alcohol (OR=1.56, 95% CI=1.36-1.89, p< 0.01) and tobacco consumption (OR=1.97, 95% CI=1.28-3.04, p< 0.01) were statistically significant, being associated with increased risk. The MTR A2756G is associated with tumor extension (OR=2.69, 95% CI=1.27-5.71, p< 0.01) and aggressiveness (OR= 4.51, 95% CI=1.67-12.1, p< 0.01). Conclusions: The MTHFR (C677T) and RFC1 (A80G) polymorphisms were involved in risk for thyroid cancer. Additionally, alcohol and tobacco consumption increase risk for disease development.