Oral cancer risk from smoking: 3X less if good CYP24A1 gene, 3X higher if poor Receptor gene - meta-analysis

Vitamin D receptor gene polymorphism in oral cancer as a function of tobacco consumption: an evidence based systematic review and meta-analysis

Front Oral Health 2025 Apr 28:6:1550683. doi: 10.3389/froh.2025.1550683

Tribikram Debata 1, Amrita Swain 1 2, Soumya Ranjan Jena 2 3, Surya Narayan Das 1, Niranjan Mishra 4, Luna Samanta 2 3

Background: The 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 methods: The 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.

Results: A 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).

Conclusion: This research underscores the role of VDR gene variants in tobacco-related oral cancer. Further studies are essential to validate findings and explore underlying mechanisms.

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