DNMT3B C46359T and SHMT1 C1420T polymorphisms in the folate pathway in carcinogenesis of head and neck

Abstract

Folate is an essential nutrient with important roles in the synthesis, repair, and DNA methylation. Polymorphisms in genes encoding enzymes involved in folate metabolism can change these processes and modulate cancer development. We investigated DNMT3B C46359T (rs2424913) and SHMT1 C1420T (rs1979277) polymorphisms related to folate pathway in head and neck cancer (HNC) risk and the association of the disease with gender, risk factors and clinical histopathological parameters. A case-control study was conducted in 725 individuals (237 patients with HNC and 488 control individuals). Real-time PCR technique was performed for genotyping. Chi square and multiple logistic regression tests were used for statistical analysis. Male gender (OR 1.80; 95% CI 1.11-2.94; P<0.02) and tobacco consumption (OR 6.14; 95% CI 4.13-9.13; P<0.001) were associated with increased risk for this neoplasia. There were no significant associations between the polymorphisms and risk of disease, however, the tobacco and alcohol habits together showed association with SHMT1 C1420T polymorphism (OR 1.48; 95% CI 1.08-2.03; P=0.014). SHMT1 C1420T polymorphism was associated with larynx tumor (OR 0.48; 95% CI 0.27-0.86; P<0.05). In conclusion, tobacco habit and male gender can be predictors for HNC risk. SHMT1 C1420T and DNMT3B C46359T polymorphisms are not associated with HNC development in Brazilian population, however, SHMT1 C1420T polymorphism is less frequent in patients with primary site of tumor in larynx and more frequent in individuals who consume tobacco and alcohol together. Further studies involving gene-gene interactions in folate pathway in different populations can contribute to the understanding of the polymorphisms effect on HNC risk.