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p16 and MGMT Methylation in Chronic Traumatic Ulcers: A Plausible Link Between Chronic Mechanical Irritation and Oral
Jeronimo Pablo Lazos1, Marcela Hernandez Rios2, Jessica Astorga2
1Oral Medicine Department, Dentistry College, Universidad Nacional de Córdoba, Córdoba, Argentina.
Background:
Chronic mechanical irritation (CMI) has been proposed as a risk factor for oral cancer. Epigenetic alterations, particularly methylation, are early events in carcinogenesis, and it has been proposed that they can be prompted by CMI. Thus, the aim of this study was to describe p16 and MGMT methylation in chronic traumatic ulcer (CTU).
Methods:
A case-control split-mouth study was performed. Two samples per individual (N = 27) were taken using exfoliative cytology using a split-mouth design, one from the CTU and the other from a contralateral site of clinically normal mucosa. DNA was extracted and bisulfite-treated, and specific sites at the promoter region of p16 and MGMT genes were amplified by qPCR using validated primers. Then, the PCR product was sequenced. The statistical analysis was performed by McNemar and the Chi-square test.
Results:
Patients had a mean age of 59.1 years. CTU showed higher methylation than control sites for both p16 (85% vs. 20%, p < 0.0001) and MGMT (80% vs. 24%, p < 0.0005).
Conclusion:
Oral mucosa subjected to continuous exposure to CMI is associated with increased methylation of p16 and MGMT. Proper management of mechanical injury factors could be an important measure for OSCC prevention. In CMI, exfoliative cytology and the split-mouth design could be useful tools to study biomarkers. However, the role of CMI in oral carcinogenesis needs more evidence focusing on the biological phenomenon.
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