MTHFD1 G1958A, BHMT G742A, TC2 C776G and TC2 A67G polymorphisms and head and neck squamous cell carcinoma risk

• Published in: Molecular biology reports Vol. 39; no. 2; pp. 887 - 893
• Main Authors: da Silva, Lidia Maria Rebolho Batista, Galbiatti, Ana Lívia Silva, Ruiz, Mariangela Torreglosa, Raposo, Luiz Sérgio, Maniglia, José Victor, Pavarino, Érika Cristina, Goloni-Bertollo, Eny Maria
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-02-2012; Springer Nature B.V
• Subjects: Animal Anatomy; Animal Biochemistry; Betaine-Homocysteine S-Methyltransferase - genetics; Biomedical and Life Sciences; Brazil - epidemiology; Carcinoma, Squamous Cell - epidemiology; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; DNA methylation; DNA Methylation - genetics; Female; Folic Acid - metabolism; Genomic Instability - genetics; Head & neck cancer; Head and Neck Neoplasms - epidemiology; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Histology; Humans; Life Sciences; Logistic Models; Male; Methylenetetrahydrofolate Dehydrogenase (NADP) - genetics; Minor Histocompatibility Antigens; Molecular biology; Morphology; Polymerase Chain Reaction; Polymorphism; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide - genetics; Risk Factors; Transcobalamins - genetics; enes; Head and neck cancer; and; Genetic polymorphism
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-011-0813-3

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.