title: MTHFD1 G1958A, BHMT G742A, TC2 C776G and TC2 A67G polymorphisms and head and neck squamous cell carcinoma risk.
abstract: Alterations in folate metabolism may contribute to the process of carcinogenesis by influencing DNA methylation and genomic stability. Polymorphisms in genes encoding enzymes involved in this pathway may alter enzyme activity and consequently interfere in concentrations of homocysteine and S-adenosylmethionine that are important for DNA synthesis and cellular methylation reactions. The objectives were to investigate MTHFD1 G1958A, BHMT G742A, TC2 C776G and TC2 A67G polymorphisms involved in folate metabolism on head and neck cancer risk and the association between these polymorphisms with risk factors. Polymorphisms were investigated in 762 individuals (272 patients and 490 controls) by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Real Time-PCR. Chi-square and Multiple logistic regression were used for the statistical analysis. Multiple logistic regression showed that tobacco and male gender were predictors for the disease (P < 0.05). Hardy-Weinberg equilibrium showed that the genotypic distributions were in equilibrium for both groups in all polymorphisms studied. The BHMT 742GA or AA genotypes associated with tobacco consumption (P = 0.016) increase the risk for head and neck squamous cell carcinoma (HNSCC). The present study suggests that BHMT 742GA polymorphism associated to tobacco modulate HNSCC risk. However, further investigation of gene-gene interactions in folate metabolism and studies in different populations are needed to investigate polymorphisms and HNSCC risk.
authors.affiliation: Genetics and Molecular Biology Research Unit (UPGEM), Department of Molecular Biology, São José do Rio Preto Medical School (FAMERP), UPGEM-Bloco U6, Avenida Brigadeiro Faria Lima, no. 5416, São José do Rio Preto, SP 15090-000, Brazil.
authors.forename: Lidia Maria Rebolho Batista
authors.initials: LM
authors.lastname: da Silva
authors.forename: Ana Lívia Silva
authors.initials: AL
authors.lastname: Galbiatti
authors.forename: Mariangela Torreglosa
authors.initials: MT
authors.lastname: Ruiz
authors.forename: Luiz Sérgio
authors.initials: LS
authors.lastname: Raposo
authors.forename: José Victor
authors.initials: JV
authors.lastname: Maniglia
authors.forename: Erika Cristina
authors.initials: EC
authors.lastname: Pavarino
authors.forename: Eny Maria
authors.initials: EM
authors.lastname: Goloni-Bertollo
mesh_terms: D050940:Betaine-Homocysteine S-Methyltransferase / Q000235:genetics*; D001938:Brazil / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation / Q000235:genetics; D005260:Female; D005492:Folic Acid / Q000378:metabolism; D042822:Genomic Instability / Q000235:genetics; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016015:Logistic Models; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics*; D015778:Minor Histocompatibility Antigens; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D014155:Transcobalamins / Q000235:genetics*
chemical_list: D015778:Minor Histocompatibility Antigens; D014155:Transcobalamins; D005492:Folic Acid; C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); C494548:BHMT protein, human; D050940:Betaine-Homocysteine S-Methyltransferase