TP53 Arg72Pro and XPD Lys751Gln Gene Polymorphisms and Risk of Lung Cancer in Bangladeshi Patients.

Tahsin Nairuz,Yearul Kabir,Mostafijur Rahman,Most Umme Bushra

doi:10.31557/apjcp.2020.21.7.2091

Abstract

Background:Tumor suppressor gene (TP53) is considered as the most frequently mutated gene in almost all forms of human cancer. Moreover, genetic variations in the XPD gene affect the DNA repair capacity increasing cancer susceptibility. Polymorphisms within these genes can play a major role in determining individual lung cancer susceptibility. However, several studies have investigated this possibility; but reported conflicting results. Therefore, the objective of this study was to investigate the role of TP53 Arg72Pro and XPD Lys751Gln gene polymorphisms on lung cancer susceptibility in the Bangladeshi population. Materials and Methods:Study subjects comprised of 180 lung cancer patients and 200 healthy volunteers. Genetic polymorphism of TP53 was determined by multiplex PCR-based method, while XPD genotypes were analyzed using Polymerase Chain Reaction-based Restriction Fragment Length Polymorphism (PCR-RFLP) method. Lung cancer risk was estimated as odds ratio (OR) and 95% confidence interval (CI). Results:From the results, no significant association between TP53 Arg72Pro polymorphism and lung cancer risk was observed. Whereas, patients with homozygous mutant variants (Gln/Gln) of XPD at codon 751 were found significantly associated with lung cancer risk when compared to the control (OR=3.58; 95% CI=1.58-8.09; p=0.002). Lung cancer risk was found significantly higher with Gln/Gln variants of XPD among smokers (OR=4.03; 95% CI=1.11-14.63; p=0.026). Significant increased risk of lung cancer was found with Arg/Pro genotypes of TP53, Lys/Gln and Gln/Gln variants of XPD in individuals with family history of cancer (OR=3.44; 95% CI=1.36-8.72; p=0.011; OR=3.17; 95% CI=1.20-8.39; p=0.024; OR=16.35; 95% CI=0.92-289.5; p=0.007, respectively). Conclusion:The findings indicated that homozygous mutant variants (Gln/Gln) of XPD were associated with increased lung cancer risk, whereas TP53 Arg72Pro polymorphism was not associated with risk of lung cancer among Bangladeshi patients.

Highlights

Lung cancer is one of the most prevalent malignancies with the largest number of patients all over the world
No significant differences were present in the frequency distribution of proline homozygous (Pro/Pro) (OR= 0.976, 95% confidence interval (CI)= 0.64-1.50, p=0.501) and arginine/proline heterozygous (Arg/Pro) (OR= 1.458, 95% confidence intervals (95% CI)= 0.60-3.55, p=0.914) between controls and lung cancer patients, when Arg/Arg was considered as reference group
tumor suppressor gene p53 (TP53) and Xeroderma Pigmentosum Complementary group D (XPD) Polymorphisms in Lung Cancer. This population-based case-control study was carried out to evaluate the association of Tumor suppressor gene p53 (TP53) and Xeroderma Pigmentosum Complementary Group D (XPD) gene polymorphisms on lung cancer susceptibility in the Bangladeshi population

Summary

Introduction

Lung cancer is one of the most prevalent malignancies with the largest number of patients all over the world. In Bangladesh, the total number of lung cancer patients was estimated to be 196,000 and 85% of those are aged 30 years or above (Hussain and Sullivan, 2013). Genetic variations in the XPD gene affect the DNA repair capacity increasing cancer susceptibility Polymorphisms within these genes can play a major role in determining individual lung cancer susceptibility. The objective of this study was to investigate the role of TP53 Arg72Pro and XPD Lys751Gln gene polymorphisms on lung cancer susceptibility in the Bangladeshi population. Patients with homozygous mutant variants (Gln/Gln) of XPD at codon 751 were found significantly associated with lung cancer risk when compared to the control (OR=3.58; 95% CI=1.58-8.09; p=0.002). Conclusion: The findings indicated that homozygous mutant variants (Gln/Gln) of XPD were associated with increased lung cancer risk, whereas TP53 Arg72Pro polymorphism was not associated with risk of lung cancer among Bangladeshi patients

Objectives

Methods

Results

Conclusion