Association between the variations in metabolic pathways and oral cancer risk: results from a Pakistani case-control study

Mol Biol Rep. 2024 Nov 19;51(1):1165. doi: 10.1007/s11033-024-10100-y.

Abstract

Background: Oral cancer (OC) is a significant global health concern, with Pakistan ranking 5th worldwide in OC incidence. Given the poor prognosis, early detection of at-risk individuals is crucial. Genetic factors, particularly single nucleotide polymorphisms (SNPs) in metabolic genes, may influence OC susceptibility. This study investigated the association between SNPs in CYP1A1, COX2, SOD2, and HIF1a genes and OC risk in the Pakistani population.

Methods: A prospective study was conducted from October 2019 to March 2022, enrolling 215 newly diagnosed OC patients and 410 controls. Genetic variations were analyzed using High-Resolution Melting (HRM) analysis and Sanger sequencing, with protein expression evaluated by ELISA.

Results: No significant associations were found between the studied SNPs and OC risk. However, a non-significant trend was observed for the SOD2 variant (rs4880), where the G allele was associated with a higher OC risk than the A allele (p = 0.20). Elevated COX2 and HIF1α levels (p-values of 0.014 and < 0.001, respectively) and reduced SOD2 levels (p < 0.0001) were observed in OC patients, while CYP1A1 levels remained similar in both controls and cases.

Conclusion: Although SNPs in CYP1A1, COX2, SOD2, and HIF1α were not significantly associated with OC risk in the Pakistani population, altered protein expression levels of COX2, HIF1α and SOD2 suggest additional regulatory mechanisms. Further investigation into post-transcriptional modifications and epigenetic factors could lead to novel biomarkers and therapeutic targets for OC in Pakistan.

Keywords: COX2; CYP1A1; HIF1α; Oral cancer; SOD2; Single nucleotide polymorphism.

MeSH terms

  • Adult
  • Aged
  • Alleles
  • Case-Control Studies
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Cytochrome P-450 CYP1A1* / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit* / genetics
  • Hypoxia-Inducible Factor 1, alpha Subunit* / metabolism
  • Male
  • Metabolic Networks and Pathways / genetics
  • Middle Aged
  • Mouth Neoplasms* / genetics
  • Mouth Neoplasms* / metabolism
  • Pakistan / epidemiology
  • Polymorphism, Single Nucleotide* / genetics
  • Prospective Studies
  • Risk Factors
  • Superoxide Dismutase* / genetics
  • Superoxide Dismutase* / metabolism

Substances

  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Superoxide Dismutase
  • CYP1A1 protein, human
  • Cytochrome P-450 CYP1A1
  • superoxide dismutase 2
  • HIF1A protein, human
  • Cyclooxygenase 2
  • PTGS2 protein, human