Influence of XPD and APE1 DNA Repair Gene Polymorphism on Bladder Cancer Susceptibility in North India

OBJECTIVES To explore the association between xerodema pigmentosum group D (XPD) Asp(312)Asn and Lys(751)Gln and apurinic apyrimidic endonuclease 1 (APE1) Asp(148)Glu gene polymorphism and risk of bladder cancer (BC) susceptibility. METHODS This hospital-based case-control study included 206 patients with newly diagnosed bladder transitional cell carcinoma and 250 cancer-free controls who had been frequency matched by age, sex, and ethnicity. Polymorphisms in XPD Asp(312)Asn and Lys(751)Gln and APE1 Asp(148)Glu gene using polymerase chain reaction-restriction fragment length polymorphisin and amplification refractory mutation system were genotyped. RESULTS The XPD Asp(312)Asn AA genotype was associated with an elevated risk of BC (odds ratio [OR] 3.30, P = .001.) The AA genotype was significantly associated with nonmuscle-invasive BC (OR 4.62, corrected P = .003). Both the heterozygous GA and the homozygous AA was associated with a greater risk of low-grade (grade 1) BC (OR 2.51, corrected P =.006 and OR 5.21, corrected P =.003, respectively). The APE1 GG genotype showed a decreased risk of BC (OR 0.27, P =.027.) Haplotype AC (codon 312A-codon 751C) of XPD demonstrated an association with a greater susceptibility to BC (OR 2.16, correct P =.0008). CONCLUSIONS Reduced DNA repair capacity due to XPD Asp(312)Asn AA genotype might be a risk factor for BC. The AA genotype predisposed to a greater risk at the initial stage and grade of BC. The APE1 148GG genotype conferred a protective association with BC susceptibility. UROLOGY 73: 675-680, 2009. (C) 2009 Elsevier Inc.