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

Abstract

Introduction: The study indicated that XPD and XPG gene polymorphism is associated with the development of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma. Xeroderma pigmentosa (XP) is a part of the complex DNA repair system. Xeroderma pigmentosum group G (XPG) and xeroderma pigmentosum group D (XPD) gene function in the nucleotide excision repair (NER) pathway. XPG and/or XPD gene alterations can cause defective DNA repair efficiency which ultimately leads to genomic instability and carcinogenesis. Thus, this study helps in early detection of OPMDs among individuals who have not yet developed any oral lesions and also helps in the management of oral squamous cell carcinoma as if XP gene polymorphism is known. Aims and Objectives: The aim of the study was to evaluate the expression of XPD and XPG gene polymorphism in oral squamous cell carcinoma cases. The study also had the objective to evaluate and compare the expression of XPG and XPD gene polymorphism in oral squamous cell carcinoma (OSCC) cases, tobacco chewers without any oral lesions, and normal healthy individuals without any habit. Materials and Method: A total of 150 subjects were included in the study and genotyped for the expression of XPD (AC) and XPG (GC) gene polymorphism using polymerase chain reaction (PCR) and agarose gel electrophoresis method. Results: XPD genotype for the study shows that most of the cases of OSCC show heterozygous (AC) genotype (64%), whereas in tobacco chewers without any oral lesions wild (AA) genotype (54%) is more common than other types. XPG genotype for the study shows that wild (GG) type is the most dominant genotype both in OSCC cases (78%) and tobacco chewers without any oral lesion (56%). Conclusion: The study shows the association of XPD and XPG gene polymorphism with the risk of developing OPMDs and oral cancer.

The association between XPD rs13181 and rs1799793 polymorphism and oral cancer risk: evidence from a meta-analysis

“…In the sensitivity analysis, each individual study included in the meta-analysis was sequentially removed to observe its influence on the pooled ORs. We found that two studies significantly affected the pooled OR value [ 8 , 10 ], suggesting relative instability in the results of this meta-analysis (Fig. 8 for allele model).…”

“…A total of one hundred and eighty-two records were identified based on the search strategy, and two additional records were added after screening reference lists. One hundred and thirteen records were screened, and twelve studies were included in this meta-analysis [ 7 , 8 , 10 – 19 ] (Fig. 1 ).…”

“…While our meta-analysis provides valuable insights, it has limitations. Sensitivity analysis revealed relative instability, possibly due to two influential studies [ 8 , 10 ], necessitating further more case-control studies. Factors such as gender, family history, environmental influences, and lifestyle, including tobacco and alcohol consumption, were not evaluated in our analysis, despite their known association with oral cancer [ 12 ].…”

“…Xeroderma pigmentosum group D (XPD), also known as excision repair cross-complementation rodent repair deficiency group 2 (ERCC2), is located on chromosome 19q13.3, comprises of 23 exons and encodes 760 amino acids [ 7 ]. The XPD gene functions in the nucleotide excision repair (NER) pathway, alterations in this gene can cause defective DNA repair efficiency, ultimately leading to genomic instability and carcinogenesis [ 8 ]. Two SNPs in XPD have been shown to be involved in susceptibility to oral cancer: codon 312 (G > A substitution at position 23,951, exon 10, Asp > Asn, rs1799793) and codon 751 (A > C substitution at nucleotide position 35,931, exon 23, Lys > Gln, rs13181) [ 9 ].…”

“…The function of Asp312Asn remains to be elucidated. Many studies have reported the association between polymorphisms of rs13181 and rs1799793 with oral cancer risk, but with conflicting and inconclusive results [ 7 , 8 , 10 – 19 ]. Thus, we performed this comprehensive meta-analysis to better illustrate the relationship between XPD polymorphism and oral cancer risk.…”