Risk Modulation of Oral Pre Cancer and Cancer with Polymorphisms in XPD and XPG Genes in North Indian Population

Asian Pac J Cancer Prev. 2019 Aug 1;20(8):2397-2403. doi: 10.31557/APJCP.2019.20.8.2397.

Abstract

Background: Environmental carcinogens cause DNA damages which if not repaired properly, may increase the risk of cancer. The Xerodermapigmentosum group D (XPD) and group G (XPG) genes are essential genes for DNA repair and alteration in DNA repair causes cancer. The present study aimed to evaluate the relationship between XPD and XPG polymorphisms and risk of oral pre cancer and cancer. Methods: Present study genotyped 302 samples of oral diseases and 300 controls for XPD (A/C) and XPG (G/C) polymorphisms with PCR-RFLP method. Results: Our result showed that compared to AA genotype frequency of AC and CC genotype for XPD(A/C) polymorphism were significantly lower among cases than in control and are associated with decreased risk of oral diseases (OR= 0.621 and 0.603 respectively). In contrast with reference to GG genotype the frequency of CC genotype of XPG (G/C) was significantly higher in case than in control population (p value=0.004) and found to increase the risk of oral diseases (OR= 2.077). Particularly C allele for XPD A/C polymorphism was found to be associated with decreased risk of Lichen planus and increased risk of ( OR = 0.470 and 1.541 respectively) oral cancer. While C allele of XPG G/C polymorphism significantly increased the risk of Oral Submucous Fibrosis and Leukoplakia (OR= 1.879 and 1.837 respectively) but not of Lichen planus and oral cancer. In combined genotype analysis from the aforesaid polymorphisms presence of C allele for XPD (A/C) polymorphisms were found to decrease the risk of oral diseases. However, the same C allele was observed to increase the chance of having high stage disease (OR= 5.71) with nodal involvement (OR= 6.78) once the cancer been initiated. Conclusion: This work shows association of XPD (A/C), XPG (G/C) polymorphisms with the development of pre oral cancer as well as oral cancer and its clinical courses.

Keywords: Oral pre cancer and cancer; PCR-RFLP; XPD; XPG; gene polymorphism.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Child
  • DNA-Binding Proteins / genetics*
  • Endonucleases / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • India / epidemiology
  • Male
  • Middle Aged
  • Mouth Neoplasms / epidemiology
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Precancerous Conditions / epidemiology
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / pathology
  • Risk Factors
  • Transcription Factors / genetics*
  • Xeroderma Pigmentosum Group D Protein / genetics*
  • Young Adult

Substances

  • DNA excision repair protein ERCC-5
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Transcription Factors
  • Endonucleases
  • Xeroderma Pigmentosum Group D Protein
  • ERCC2 protein, human