Influence of XPD and APE1 DNA repair gene polymorphism on bladder cancer susceptibility in north India.
OBJECTIVE
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 polymorphism 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.
Gangwar
Ruchika
R
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Ahirwar
Dinesh
D
Mandhani
Anil
A
Mittal
Rama Devi
RD
D002295:Carcinoma, Transitional Cell / Q000235:genetics*; D016022:Case-Control Studies; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D001749:Urinary Bladder Neoplasms / Q000235:genetics*; D051759:Xeroderma Pigmentosum Group D Protein / Q000235:genetics*
D051759:Xeroderma Pigmentosum Group D Protein; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; C497292:ERCC2 protein, human