title: Influence of MTHFR Genetic Background on p16 and MGMT Methylation in Oral Squamous Cell Cancer.
abstract: Genetic polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) enzyme may influence DNA methylation. Alterations in DNA methylation patterns of genes involved in the regulation of the cell cycle, DNA repair, cell adherence and metastasis process are known to contribute to cancer development. In this study, the influence of the MTHFR C677T and A1298C gene polymorphisms on global DNA methylation and site-specific methylation onp16andO⁶-methylguanine-DNA methyltransferase (MGMT) gene promoters was investigated in patients with oral squamous cell cancer (OSCC). To this aim, methylation studies were carried out by using genomic DNA isolated from saliva samples of 58 OSCC patients and 90 healthy controls. The frequency of the CT/AC and TT/AA genotypes was significantly higher in patients than in controls. Whereas no difference in global DNA methylation levels was observed between patients and controls, a higher frequency of methylation at bothp16andMGMTgene promoters was detected in patients compared with controls. A significant association betweenMTHFRgene polymorphisms andp16andMGMTgene promoter methylation was found. The frequency ofp16andMGMTmethylation was around 60% in patients with either the CT/AC or TT/AA genotype. Our results suggest that hypermethylation of cancer-related genes may be affected byMTHFRpolymorphisms.
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98124 Messina, Italy. nferlazzo@unime.it.
authors.forename: Nadia
authors.initials: N
authors.lastname: Ferlazzo
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98124 Messina, Italy. moncurro@unime.it.
authors.forename: Monica
authors.initials: M
authors.lastname: Currò
authors.affiliation: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy. azinellu@uniss.it.
authors.forename: Angelo
authors.initials: A
authors.lastname: Zinellu
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98124 Messina, Italy. dcaccamo@unime.it.
authors.forename: Daniela
authors.initials: D
authors.lastname: Caccamo
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98124 Messina, Italy. gisola@unime.it.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Isola
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98124 Messina, Italy. valeriaventura82@hotmail.it.
authors.forename: Valeria
authors.initials: V
authors.lastname: Ventura
authors.affiliation: Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy. carru@uniss.it.|Control Quality Unit, University Hospital of Sassari (AOU), 07100 Sassari, Italy. carru@uniss.it.
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Carru
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98124 Messina, Italy. gmatarese@unime.it.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Matarese
authors.affiliation: Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98124 Messina, Italy. ientile@unime.it.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Ientile
mesh_terms: D000328:Adult; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics*; D045643:DNA Repair Enzymes / Q000235:genetics*; D005260:Female; D019942:Genes, p16; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D025521:Tumor Suppressor Proteins; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: MGMT promoter methylation; MTHFR polymorphisms; global DNA methylation; oral squamous cell cancer; p16 promoter methylation