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ASSOCIATION OF DNA METHYLATION AND ORAL CANCER RISK: A SYSTEMATIC REVIEW AND META-ANALYSIS.

Óscar Rapado-González1, Cristina Isabel Sevilla-García2, Juan Pizcueta-Leirós2

  • 1Department of Surgery and Medical-Surgical Specialties, Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela 15782, Spain; Galician Precision Oncology Research Group (ONCOGAL), Medicine and Dentistry School, Universidade de Santiago de Compostela (USC), Santiago de Compostela, Spain; Liquid Biopsy Analysis Unit, Translational Medical Oncology Group (ONCOMET), Health Research Institute of Santiago (IDIS), Santiago de Compostela 15706, Spain; Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid 28029, Spain; Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/CI-IPOP@RISE (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Center Raquel Seruca (Porto.CCC), Porto 4200-072, Portugal; International Iberian Nanotechnology Laboratory (INL), Medical Devices Research Group, Braga 4715-330, Portugal.

The Journal of Evidence-Based Dental Practice
|November 25, 2025
PubMed
Summary

DNA promoter methylation is significantly associated with oral cancer (OC) risk. Specific gene promoter methylation, including p16 and ECAD, plays a key role in oral carcinogenesis and may serve as biomarkers for OC.

Keywords:
BiomarkersDNA methylationEpigeneticsMeta-analysisOdds ratioOral cancer

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Area of Science:

  • Oncology
  • Epigenetics
  • Genetics

Background:

  • DNA promoter methylation is a key epigenetic mechanism for tumor-suppressor gene silencing in cancer.
  • Aberrant DNA methylation is observed in oral cancer (OC), but its association with OC risk is debated.

Purpose of the Study:

  • To assess the overall and specific impact of DNA promoter methylation on the risk of developing oral cancer.

Main Methods:

  • A systematic literature search was conducted across PubMed, EMBASE, Web of Science, and Cochrane Library.
  • Meta-analysis of 41 case-control studies (4218 OC patients, 3478 controls) was performed using R software.
  • Newcastle-Ottawa Scale assessed study quality; Egger's test detected publication bias.

Main Results:

  • A significant overall association exists between DNA promoter methylation and OC risk (OR = 5.83).
  • Specific genes showed significant associations: p16 (OR=5.77), ECAD (OR=4.47), MGMT (OR=3.85), DAPK (OR=5.58), hMLH1 (OR=10.48), p14 (OR=3.21), and p15 (OR=5.02).

Conclusions:

  • Gene promoter methylation is significantly linked to oral cancer risk.
  • Methylation of p16, ECAD, MGMT, DAPK, hMLH1, p15, and p14 are implicated in oral carcinogenesis.
  • These methylated genes show promise as biomarkers for oral cancer prediction and prognosis.