AUTHOR=Debata Tribikram , Swain Amrita , Jena Soumya Ranjan , Das Surya Narayan , Mishra Niranjan , Samanta Luna TITLE=Vitamin D receptor gene polymorphism in oral cancer as a function of tobacco consumption: an evidence based systematic review and meta-analysis JOURNAL=Frontiers in Oral Health VOLUME=Volume 6 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/oral-health/articles/10.3389/froh.2025.1550683 DOI=10.3389/froh.2025.1550683 ISSN=2673-4842 ABSTRACT=BackgroundThe association between Vitamin D Receptor (VDR) polymorphisms and different cancers has attracted growing attention; nonetheless, the function of these genetic variants in tobacco-related oral cancer remains little comprehended. This review assesses and integrates research concerning the influence of VDR gene variants on the development of tobacco-related oral cancer, emphasizing genetic underpinnings of individual vulnerability and possible tailored preventative approaches.Materials and methodsThe search strategy for this systematic review and meta-analysis was devised to comprehensively identify relevant studies from diverse sources. The investigation included three primary components: the VDR gene, oral cancer, and tobacco. The data from the papers included in the study were independently retrieved by two reviewers. The incidence was evaluated as an odds ratio (OR) with 95% confidence interval (95% CI) using SPSS software.ResultsA preliminary search of biomedical electronic research databases (PubMed, Web of Science, Scopus, Embase, and the Cochrane Library) yielded 60,345 papers. After multi-phase exclusions, five studies met the inclusion criteria. The meta-analysis highlights interactions between genetic polymorphisms, smoking, aging, and oral health risks. The CYP24A1 (rs2296241) heterozygote genotype significantly reduces oral cancer risk (OR = 0.281, P = 0.00001). Variants rs1544410 and rs2228570 influence oral health outcomes. The rs2239185 TT (OR = 2.68, P = 0.009) and rs7975232 CC (OR = 2.25, P = 0.026) increase oral lichen planus risk. Older age is significantly linked to OSCC risk (P = 0.001).ConclusionThis research underscores the role of VDR gene variants in tobacco-related oral cancer. Further studies are essential to validate findings and explore underlying mechanisms.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD42024587292, identifier: CRD42024587292.