Polymorphic variants of DNA repair gene XRCC3 and XRCC7 and risk of prostate cancer: a study from North Indian population.
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.
Mandal
Raju K
RK
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, India.
Kapoor
Rakesh
R
Mittal
Rama Devi
RD
D044466:Asian People / Q000235:genetics*; D001859:Bone Neoplasms / Q000556:secondary; D016022:Case-Control Studies; D015331:Cohort Studies; D004260:DNA Repair / Q000235:genetics*; D051747:DNA-Activated Protein Kinase / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007194:India; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D012907:Smoking
D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C110901:X-ray repair cross complementing protein 3; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human