C677T and A1298C polymorphisms of methylene tetrahydrofolate reductase in non-Hodgkin lymphoma: southeast Iran

Abstract

Purpose: Polymorphisms of the methylene tetrahydrofolate reductase (MTHFR) gene have been reported as risk factors for non-Hodgkin lymphoma (NHL) in some populations. Our goal was to evaluate the potential role of A1298C and C677T polymorphisms of MTHFR in risk of NHL in southeast Iran. Methods: In the present case-control study, 127 patients with newly diagnosed NHL along with 150 ethnicity- and age-matched controls were examined. The A1298C and C677T polymorphisms were genotyped using the Tetra Amplification Refractory Mutation System polymerase chain reaction method. Results: There were no significant differences in genotype frequencies between cases and controls regarding either A1298C polymorphism. For this polymorphism, 53.8% of the controls and 54.3% of the patients with NHL showed homozygous wild-type (AA) genotype. Variant 1298C allele was recognized with overall frequency of 34.6% in both groups. Frequencies of CC, CT, and TT genotypes of C677T polymorphism were observed in 73.1%, 25.8%, and 1.3% of the controls, and 64.5%, 33.1%, and 2.4% of the patients with NHL (p>0.05). In combination, CT + TT conferred a significantly higher risk of NHL (odds ratio [OR] 1.5, 95% confidence interval [CI] 0.9-2.4, p = 0.03). Overall, variant 677T allele presented with higher frequency in the patients with NHL than the controls (26.7% versus 21.3%, respectively; OR 1.3, 95% CI 0.8-2.1, p>0.05). Although statistically insignificant, the highest risk of NHL was identified in patients with C677T; A1298C: CT; CC haplotype (OR 4.7, 95% CI 0.4-46.4, p = 0.1). Conclusions: Combination of CT and TT genotypes of C677T polymorphism conferred a significantly higher risk for NHL. It is recommended to investigate further the potential role of this polymorphism in NHL development.