title: 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.
authors.affiliation: Molecular Biology Research Unit (UPGEM), Molecular Biology Department Genetic, São José do Rio Preto Medical School (FAMERP), Bloco U6. Avenida Brigadeiro Faria Lima, No. 5416, Vila São Pedro, São José do Rio Preto, 15090-000, SP, Brazil.
authors.forename: Maysa
authors.initials: M
authors.lastname: Succi
authors.forename: Tialfi Bergamin
authors.initials: TB
authors.lastname: de Castro
authors.forename: Ana Lívia Silva
authors.initials: AL
authors.lastname: Galbiatti
authors.forename: Lidia Maria Rebolho Batista
authors.initials: LM
authors.lastname: Arantes
authors.forename: Jéssika Nunes Gomes
authors.initials: JN
authors.lastname: da Silva
authors.forename: José Victor
authors.initials: JV
authors.lastname: Maniglia
authors.forename: Luiz Sérgio
authors.initials: LS
authors.lastname: Raposo
authors.forename: Erika Cristina
authors.initials: EC
authors.lastname: Pavarino
authors.forename: Eny Maria
authors.initials: EM
authors.lastname: Goloni-Bertollo
mesh_terms: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D001938:Brazil; D063646:Carcinogenesis / Q000235:genetics*; D016022:Case-Control Studies; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D056726:Genetic Association Studies; D005838:Genotype; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics*; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D000097584:DNA Methyltransferase 3B
chemical_list: D004248:DNA (Cytosine-5-)-Methyltransferases; D005492:Folic Acid; D012696:Glycine Hydroxymethyltransferase; D000097584:DNA Methyltransferase 3B; C520541:SHMT protein, human