Polymorphisms in , , and genes involved in folate metabolism and thyroid cancer: a case-control study.

INTRODUCTION

Polymorphisms in genes coding enzymes involved in folate metabolism may cause alterations in this metabolic pathway and contribute to carcinogenesis, because folate is essential for DNA synthesis, methylation and repair. The objective of this study was to investigate the association of 677C>T (rs1801133), 2756A>G (rs1805087), 80A>G (rs1051266) and 844ins(68) (no rs#) polymorphisms and thyroid cancer development. The association of these polymorphisms with demographic risk factors and clinical histopathological parameters was also evaluated.

MATERIAL AND METHODS

The study is a case-control analysis with a total of 462 individuals (151 patients and 311 controls). Polymerase chain reaction-restriction fragment length polymorphism technique was used for genotyping. The χ and multiple logistic regression were utilized for statistical analysis.

RESULTS

The polymorphisms analysis revealed an association between the 677C>T polymorphism (OR = 2.87, 95% CI: 1.50-5.48, < 0.01, codominant model), (OR = 1.76, 95% CI: 1.18-2.64, < 0.01, dominant model), (OR = 2.37, 95% CI: 1.28-4.39, < 0.01, recessive model) and thyroid cancer. 80A>G polymorphism also was associated with thyroid cancer under recessive mode of inheritance (OR = 1.55; 95% CI: 1.02-2.38; = 0.04); however, this polymorphism showed Hardy-Weinberg disequilibrium in the control group (χ = 24.71, < 0.001). Furthermore, alcohol (OR = 1.56, 95% CI: 1.36-1.89, < 0.01) and tobacco consumption (OR = 1.97, 95% CI: 1.28-3.04, < 0.01) were associated with increased risk for thyroid cancer. The 2756A>G polymorphism showed an association with tumor extent (OR = 2.69, 95% CI: 1.27-5.71, < 0.01) and aggressiveness (OR = 4.51, 95% CI: 1.67-12.1, < 0.01).

CONCLUSIONS

677C>T is significantly associated with increased risk for thyroid cancer and 2756A>G is associated with tumor extent and aggressiveness. In addition, alcohol and tobacco consumption were associated with increased risk of thyroid cancer. These results may contribute to a better prognosis for thyroid cancer.