title: Polymorphisms in base-excision & nucleotide-excision repair genes & prostate cancer risk in north Indian population.
abstract: OBJECTIVE
  Genetic variation in the DNA repair genes might be associated with altered DNA repair capacities (DRC). Reduced DRC due to inherited polymorphisms may increase the susceptibility to cancers. Base excision and nucleotide excision are the two major repair pathways. We investigated the association between two base excision repair (BER) genes (APE1 exon 5, OGG1 exon 7) and two nucleotide excision repair (NER) genes (XPC PAT, XPC exon 15) with risk of prostate cancer (PCa).
  
  
  METHODS
  The study was designed with 192 histopathologically confirmed PCa patients and 224 age matched healthy controls of similar ethnicity. Genotypes were determined by amplification refractory mutation specific (ARMS) and PCR-restriction fragment length polymorphism (RFLP) methods.
  
  
  RESULTS
  Overall, a significant association in NER gene, XPC PAT Ins/Ins (I/I) genotype with PCa risk was observed (Adjusted OR- 2.55, 95%CI-1.22-5.33, P=0.012). XPC exon 15 variant CC genotypes presented statistically significant risk of PCa (Adjusted OR- 2.15, 95% CI-1.09-4.23, P=0.026). However, no association was observed for polymorphism with BER genes. Diplotype analysis of XPC PAT and exon 15 revealed that the frequency of the D-C and I-A diplotype was statistically significant in PCa. The variant genotypes of NER genes were also associated with high Gleason grade.
  
  
  CONCLUSIONS
  The results indicated that there was a significant modifying effect on the association between genotype XPC PAT and exon 15 polymorphism and PCa risk which was further confirmed by diplotype analysis of XPC PAT and exon 15 in north Indian population.
authors.affiliation: Department of Urology & Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Raju K
authors.initials: RK
authors.lastname: Mandal
authors.forename: Ruchika
authors.initials: R
authors.lastname: Gangwar
authors.forename: Rakesh
authors.initials: R
authors.lastname: Kapoor
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D000368:Aged; D045647:DNA Glycosylases / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005091:Exons; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D054643:INDEL Mutation; D007194:India; D007438:Introns; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D004268:DNA-Binding Proteins; C086984:XPC protein, human; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase