Frontiers in oral health · 2026
VDR polymorphisms and their influence on oral squamous cell carcinoma susceptibility: a systematic review.
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Hegde Mithra N, Nireeksha, Somanatha Harshitha, Hegde Nishmitha N, Ravinanthanan Manikandan, Balan Usha
Аннотация
BACKGROUND: Oral Squamous Cell Carcinoma (OSCC) arises through an intricate interplay of underlying genetic traits and surrounding environmental conditions. Variations in the vitamin D receptor (VDR) gene, particularly single-nucleotide polymorphisms (SNPs), may contribute to individual susceptibility and disease progression.
OBJECTIVE: To conduct a systematic review evaluating the role of VDR gene polymorphisms in influencing susceptibility to OSCC.
METHODS: A systematic literature search was performed in PubMed, Scopus, and Google Scholar to identify human case-control studies evaluating VDR SNPs in relation to OSCC. The methodological quality and potential bias of the selected studies were assessed using the Newcastle-Ottawa Scale (NOS). Due to substantial heterogeneity among the studies in terms of population characteristics, genotyping methods, and outcome measures, a meta-analysis was not performed, and the findings were summarized descriptively.
RESULTS: From an initial pool of 90 records, five case-control studies met the inclusion criteria. Qualitative synthesis revealed consistent associations between polymorphisms in the VDR gene, particularly Fok1 (rs2228570), TaqI (rs731236), and ApaI (rs7975232), and in the CYP24A1 (rs2296241) gene, which encodes a VDR-regulated enzyme involved in the catabolism of active vitamin D metabolites. These variants have also been explored for their potential association with oral potentially malignant disorders (OPMDs), including leukoplakia, oral submucous fibrosis, and oral erythroplakia, which may undergo malignant transformation to OSCC. Most of the included studies demonstrated a low risk of bias and supported the role of these SNPs in OSCC susceptibility, as well as their potential prognostic relevance.
CONCLUSION: VDR polymorphisms may contribute to OSCC risk by affecting immune and cellular pathways. Although findings are promising, larger, multi-ethnic studies are needed to confirm their clinical significance.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251105619, PROSPERO CRD420251105619.
OBJECTIVE: To conduct a systematic review evaluating the role of VDR gene polymorphisms in influencing susceptibility to OSCC.
METHODS: A systematic literature search was performed in PubMed, Scopus, and Google Scholar to identify human case-control studies evaluating VDR SNPs in relation to OSCC. The methodological quality and potential bias of the selected studies were assessed using the Newcastle-Ottawa Scale (NOS). Due to substantial heterogeneity among the studies in terms of population characteristics, genotyping methods, and outcome measures, a meta-analysis was not performed, and the findings were summarized descriptively.
RESULTS: From an initial pool of 90 records, five case-control studies met the inclusion criteria. Qualitative synthesis revealed consistent associations between polymorphisms in the VDR gene, particularly Fok1 (rs2228570), TaqI (rs731236), and ApaI (rs7975232), and in the CYP24A1 (rs2296241) gene, which encodes a VDR-regulated enzyme involved in the catabolism of active vitamin D metabolites. These variants have also been explored for their potential association with oral potentially malignant disorders (OPMDs), including leukoplakia, oral submucous fibrosis, and oral erythroplakia, which may undergo malignant transformation to OSCC. Most of the included studies demonstrated a low risk of bias and supported the role of these SNPs in OSCC susceptibility, as well as their potential prognostic relevance.
CONCLUSION: VDR polymorphisms may contribute to OSCC risk by affecting immune and cellular pathways. Although findings are promising, larger, multi-ethnic studies are needed to confirm their clinical significance.
SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/view/CRD420251105619, PROSPERO CRD420251105619.