DNA repair gene polymorphism (XPA and XPG) and risk of urinary bladder cancer in North-Indian population

Abstract

PurposeTo assess XPA A23G (rs1800975) and XPG Asp1104His (rs17655) polymorphism as risk factors for urinary bladder cancer in North-Indian population. MethodsThe prevalence of genetic polymorphisms of XPA and XPG was investigated in cases and age-gender matched healthy controls. XPA and XPG genes were genotyped using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. ResultsThe XPA GG and XPG CC genotypes were significantly associated with UBC risk (adjusted OR = 3.78, 95% CI = 1.40-10.18, p ≤ 0.05 and adjusted OR = 4.00, 95% CI = 1.19-13.43, p ≤ 0.05 respectively). After stratifying the genotypes by age, gender and smoking status, risk for carriers of XPA (AG + GG) genotype was significantly higher for males and smokers (adjusted OR = 2.55, 95% CI = 1.30–5.03, adjusted OR = 2.36, 95% CI = 1.14–4.85, p ≤0.05 respectively) while the risk for carriers of the XPG (GC + CC) genotype was significantly high for younger (median age ≤60) individuals and females (adjusted OR = 2.13, 95% CI = 1.05–4.35, adjusted OR = 18.12, 95% CI = 1.20–272.73, p ≤0.05 respectively). ConclusionXPA and XPG polymorphism might be significant risk factor in North-Indian population and acquisition of these genetic variations together with smoking might trigger urinary bladder cancer development. Further pathway based studies on larger population are warranted to confirm our conclusion. Clinical significanceThe XPA-A23G and XPG-Asp1104His genetic variations could be used as UBC susceptibility markers in North-Indian population. These SNPs could be useful biomarkers for UBC prognosis or diagnosis and thus could help in enhancing the survival rates of UBC patients and improving patient care. However, before making any further conclusion, we suggest these genetic variations should be further explored using a larger study sample for their role as potential clinical biomarkers or therapeutic targets. The role of other SNPs, gene-gene interactions and gene-environment interactions should also be taken into consideration while estimating the genetic risk of these SNPs on UBC development.