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

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.

Comparative evaluation of XPD and XPG gene polymorphism in oral squamous cell carcinoma and tobacco chewers

“…[ 25 ] and the meta-analysis by Flores-Obando RE et al . [ 26 ] and Zhang et al ,[ 27 ] and the case–control study by Avci, Iplik, Aydemir et al ,[ 28 ] and Nigam et al [ 20 ] All of these studies suggested that polymorphism in the XPD gene could play a role in the development of OSCC [ Table 1 ].…”

“…About 98% of the normal healthy individuals show no polymorphism. The XPG gene harboured SNPs and many of the SNPs alter the risk of different cancers such as colorectal, lung, and laryngeal cancer as reported from the study done by Nigam et al [ 20 ] [ Table 2 ].…”

“…Polymorphisms of XPD and XPG genes may have synergistic effects on the development of OSCC. [ 20 ] It would also be important to elucidate possible association of the polymorphisms of the XP genes with altered functions and a cancer risk. [ 9 ]…”

Association of snps of aif-1 gene with susceptibility to oral cancer in chinese population

“…Previous studies have found a negative correlation between BMI levels and 8-OHdG levels in the body. Low body weight may increase the oxidative damage of DNA by smoking and other factors (Nigam et al, 2019;Tang et al, 2018a, b;Chang et al, 2016), thereby promoting tumorigenesis.…”

XPD inhibits cell growth and invasion and enhances chemosensitivity in esophageal squamous cell carcinoma by regulating the PI3K/AKT signaling pathway

“…A previous study found that XPd gene polymorphism increases the risk of lung cancer in residents of coal mines (8). XPD polymorphisms are associated with the development of pre oral cancer as well as oral cancer and its clinical course (9). It has been found that XPd can inhibit the proliferation and migration of hepatocellular carcinoma cells (10).…”