RT Journal Article T1 Association of DNA methylation and oral cancer risk: A systematic review and meta-analysis A1 Rapado González, Óscar A1 Sevilla-García, Cristina Isabel A1 Pizcueta Leirós, Juan A1 Salgado Barreira, Ángel A1 Piñeiro Lamas, María A1 Carlos-Villafranca, Félix de A1 López López, Rafael A1 Suárez Cunqueiro, María Mercedes K1 Oral cancer K1 DNA methylation K1 Epigenetics K1 Meta-analysis AB Background: DNA promoter methylation is one of the main epigenetic mechanisms of silencing of tumour-suppressor genes in cancer. Accumulating scientific evidence has shown various genes with aberrant DNA methylation in oral cancer, however, the magnitude of the association between DNA methylation and oral cancer (OC) risk remains controversial.Objective: To evaluate the overall and specific impact of DNA promoter methylation on the risk of oral cancer development.Material and methods: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for eligible studies. The Newcastle-Ottawa Scale (NOS) was used to evaluate the methodological quality of the included studies with a case-control design. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations with R software; and Egger’s test were used to detect publication bias.Results: A total of 41 studies including 4218 OC patients and 3478 non-cancer controls were englobed in the meta-analysis. Overall, a significant association was found between DNA promoter methylation and oral cancer risk (OR=4.81, 95% CI, 3.85—6.0; p<.001). In addition, the pooled ORs showed a significant association between specific tumor-related genes and oral cancer risk: p16 (5.77; 95% CI = 3.95–8.45; p<.001), ECAD (4.47; 95% CI = 2.77–7.21; p<.001), MGMT (3.85; 95%CI = 2.48–5.97; p<.001), DAPK (5.58; 95%CI = 2.14–14.56; p<.001), hMLH1 (OR=10.48; 95%CI = 1.04–106.1; p=.047), p14 (3.22; 95%CI = 1.79–5.79; p<.001), and p15 (4.73; 95% CI = 2.61–8.56; p<.001).Conclusion: A significant overall association was found between gene promoter methylation and oral cancer risk. Specifically, the promoter methylation of p16, ECAD, MGMT, DAPK, hMLH1, p15 and p14 displayed a significant role in oral carcinogenesis, acting as promising biomarkers for oral cancer prediction and prognosis. PB Elsevier YR 2025 FD 2025 LK https://hdl.handle.net/10347/39946 UL https://hdl.handle.net/10347/39946 LA eng NO This research was funded by Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain [grant number CB16/12/00328] and Consello Social da Universidade de Santiago de Compostela, Galicia, Spain [grant number 2021-PU007]. O.R.-G. is funded by a postdoctoral fellowship from Axencia Galega de Innovacion (GAIN), Programa de ayudas a la etapa posdoctoral de la Xunta de Galicia (IN606B-2022/007). DS Minerva RD 28 abr 2026