Do DNA repair genes OGG1, XRCC3 and XRCC7 have an impact on susceptibility to bladder cancer in the North Indian population?
OBJECTIVE
Polymorphisms in DNA repair genes may be associated with altered DNA repair capacity, thereby influencing an individual's susceptibility to smoking-related cancers such as bladder cancer. Therefore, we sought to examine the correlation between single nucleotide polymorphisms in DNA repair genes and bladder cancer.


METHODS
We undertook a case-control study of 212 urothelial bladder cancer (UBC) cases and 250 controls to investigate the association between OGG1 (C1245G rs1052133), XRCC3 (C18067T, rs861539) and XRCC7 (G6721T, rs7003908) polymorphisms and bladder cancer susceptibility by PCR-RFLP and the ARMS method. We also investigated gene-environment interactions.


RESULTS
The OGG1 GG genotype was associated with an elevated risk of urothelial bladder cancer (UBC) (OR, 2.10; p, 0.028). XRCC7 + 6721 GG was also associated with increased susceptibility to UBC (OR, 4.45; p, 0.001). In a recessive model, the OGG1 GG genotype showed an increased risk of TaG(2,3) + T1G(1-3) tumors. Additionally, the OGG1 GG genotype in non-smokers represented a 2.46-fold greater risk (OR, 2.46; p, 0.035) in bladder cancer patients. Subsequent analysis demonstrated more pronounced association of XRCC7 with smokers (OR, 4.39; p, 0.001). XRCC7 also showed increased association with TaG(2,3) + T1G(1-3) tumors and muscle invasive tumors (OR, 3.16; p, 0.001 and OR, 4.24; p, 0.001, respectively). Multiple Cox regression analysis in non-muscle invasive bladder tumor (NMIBT) patients demonstrated an association of the OGG1 GG polymorphism with a high risk of recurrence in patients on cystoscopic surveillance (HR, 4.04; p, 0.013). Subsequently, shorter recurrence-free survival (log rank p, 0.024; CC/GG, 42/24) was observed.


CONCLUSIONS
Our data suggest association of a variant (GG) genotype of OGG1 with increased UBC susceptibility and a high risk of tumor recurrence in NMIBT patients on cystoscopic surveillance. XRCC7 G allele carriers (TG+GG) are also at an elevated risk for susceptibility to UBC as evidenced by a high odds ratio throughout the analysis.
Gangwar
Ruchika
R
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow 226014, Uttar Pradesh, India.
Ahirwar
Dinesh
D
Mandhani
Anil
A
Mittal
Rama Devi
RD
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016022:Case-Control Studies; D045647:DNA Glycosylases / Q000235:genetics*; D051747:DNA-Activated Protein Kinase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000473:pathology
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110901:X-ray repair cross complementing protein 3; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human