Base excision repair pathway genes polymorphism in prostate and bladder cancer risk in North Indian population.
OBJECTIVE
Carcinogens causes DNA damage, including oxidative lesions that are removed efficiently by the base excision repair (BER) pathway. Variations in BER genes may reduce DNA repair capacity, leading to development of urological cancers.


METHODS
This study included 195 prostate cancer (PCa) and 212 bladder cancer (BC) patients and 250 controls who had been frequency matched by age, sex, and ethnicity. We genotyped XRCC1 Exon 6 (C>T), 9 (G>A), 10 (G>A), OGG1 Exon 7 (C>G) and APE1 Exon 5 (T>G) genes polymorphism using PCR-RFLP and ARMS.


RESULTS
GA of XRCC1 Exon 9 demonstrated increased risk with PCa as well as in BC (p=0.001; p=0.006). Similarly variant containing genotype revealed association with PCa (p=0.031). Haplotype of XRCC1 also associated with significant risk for PCa and BC. The APE1 GG genotype showed a decreased risk of BC (OR=0.25; p=0.017). Variant genotype GG of OGG1 demonstrated significant risk with BC (p=0.028).


CONCLUSIONS
Our observations suggested increased risk for PCa and BC in case of GA genotype for XRCC1, and variant GG in case of OGG1. However APE1 GG genotype conferred a protective association with BC susceptibility. Larger studies and the more SNPs in the same pathway are needed to verify these findings.
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, Uttar Pradesh, India. ramamittal@gmail.com
Rama Devi
RD
Mittal
Raju Kumar
RK
Mandal
Ruchika
R
Gangwar
D000368:Aged; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D045647:DNA Glycosylases / Q000235:genetics; D004260:DNA Repair; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D016017:Odds Ratio; D010641:Phenotype; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000208:ethnology; D001749:Urinary Bladder Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D000076105:X-ray Repair Cross Complementing Protein 1
D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase