Polymorphic variants of DNA repair gene XRCC3 and XRCC7 and risk of prostate cancer: a study from North Indian population

DNA Cell Biol. 2010 Nov;29(11):669-74. doi: 10.1089/dna.2010.1047. Epub 2010 Jun 30.

Abstract

DNA repair gene alterations may cause a reduction in DNA repair capacity and influence an individual's susceptibility to carcinogenesis. We hypothesized that single nucleotide polymorphisms of DNA repair genes may be a risk factor for prostate cancer (PCa) susceptibility, influencing expression of homologous recombination (XRCC3) and nonhomologous end-joining (XRCC7) genes and conferring predisposition to PCa. In a case-control study, genotyping was done in 192 patients with PCa and 224 age matched unrelated healthy controls of similar ethnicity to determine variants in XRCC3 Exon 7 (C18067T, rs861539), IVS5-14 (A17893G, rs1799796), and XRCC7 Intron 8 (G6721T, rs7003908) by polymerase chain reaction-restriction fragment-length polymorphism methods. Variant genotype GG (odds ratio [OR], 2.23; p=0.003) and combined genotype TG+GG (OR, 1.541; p=0.049), G allele of XRCC7 Intron 8 (G>T), demonstrated significant risk for PCa (OR, 1.529; p=0.002). Stratification on bases of Gleason grade and bone metastasis, significant risk with high Gleason grade for CT genotype of XRCC3 Exon 7, and variant genotype GG of XRCC7 Intron 8 were observed. Our results strongly support that common sequence variants (GG) genotype of XRCC7 may increase risk of PCa. G allele being a risk allele in our study also suggests that this polymorphism be used as a marker for the PCa susceptibility.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People / genetics*
  • Bone Neoplasms / secondary
  • Case-Control Studies
  • Cohort Studies
  • DNA Repair / genetics*
  • DNA-Activated Protein Kinase / genetics*
  • DNA-Binding Proteins / genetics*
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • India
  • Male
  • Middle Aged
  • Nuclear Proteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Prostatic Neoplasms / genetics*
  • Prostatic Neoplasms / pathology
  • Smoking

Substances

  • DNA-Binding Proteins
  • Nuclear Proteins
  • X-ray repair cross complementing protein 3
  • DNA-Activated Protein Kinase
  • PRKDC protein, human