Rapado González, ÓscarSevilla-García, Cristina IsabelPizcueta Leirós, JuanSalgado Barreira, ÁngelPiñeiro Lamas, MaríaCarlos-Villafranca, Félix deLópez López, RafaelSuárez Cunqueiro, María Mercedes2025-02-272025-02-272025https://hdl.handle.net/10347/39946Background: 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.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Oral cancerDNA methylationEpigeneticsMeta-analysis24 Ciencias de la vidajournal article1532-3390embargoed access