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Int. J. Mol. Sci. 2017, 18(4), 724; doi:10.3390/ijms18040724

Influence of MTHFR Genetic Background on p16 and MGMT Methylation in Oral Squamous Cell Cancer

1
Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98124 Messina, Italy
2
Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
3
Control Quality Unit, University Hospital of Sassari (AOU), 07100 Sassari, Italy
*
Author to whom correspondence should be addressed.
Academic Editor: Yogesh Kumar Vashist
Received: 14 February 2017 / Revised: 25 March 2017 / Accepted: 27 March 2017 / Published: 29 March 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
View Full-Text   |   Download PDF [247 KB, uploaded 29 March 2017]

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 on p16 and O6-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 both p16 and MGMT gene promoters was detected in patients compared with controls. A significant association between MTHFR gene polymorphisms and p16 and MGMT gene promoter methylation was found. The frequency of p16 and MGMT methylation 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 by MTHFR polymorphisms. View Full-Text
Keywords: oral squamous cell cancer; MTHFR polymorphisms; global DNA methylation; p16 promoter methylation; MGMT promoter methylation oral squamous cell cancer; MTHFR polymorphisms; global DNA methylation; p16 promoter methylation; MGMT promoter methylation
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Ferlazzo, N.; Currò, M.; Zinellu, A.; Caccamo, D.; Isola, G.; Ventura, V.; Carru, C.; Matarese, G.; Ientile, R. Influence of MTHFR Genetic Background on p16 and MGMT Methylation in Oral Squamous Cell Cancer. Int. J. Mol. Sci. 2017, 18, 724.

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