title: The codon 399 Arg/Gln XRCC1 polymorphism is associated with lung cancer in Indians.
abstract: BACKGROUND
  The XRCC1 (X-ray repair cross complimenting group-I) gene in BER (base excision repair) pathway is essential for DNA repair process. Polymorphisms in this gene are associated with variations in the repair efficiency which might predispose individuals to development of various cancers. Two variants of XRCC1gene (at codon 399), Gln/Gln and Arg/Gln, have been shown to be related to lowered DNA repair capacity and increased genomic instability in multiple studies. Hence our investigation focused on genotyping these variants to correlate with other multiple risk factors in lung cancer (NSCLC) patients since we hypothesized that these variants of the XRCC1 gene might influence disease susceptibility.
  
  
  METHODS
  We examined the frequency of the polymorphism in one hundred cases and an almost equal number of controls after recording their demographics with a structured questionnaire. Genomic DNA from blood samples was extracted for PCR studies, followed by RFLP to determine the variants. The significance of the data was statistically analyzed.
  
  
  RESULTS
  The three genotypes in cases and controls were Arg/Arg (40% and 54.45%); Gln/Gln (19% and 9.90%), and Arg/Gln (41.0% and 35.64%) respectively. Among these 3 genotypes, we found Gln/Gln and Arg/Gln to show association with lung cancer. Correlating these genotypes with several parameters, we also found that these two variants were associated with risk in males (p<0.05) and with smoking habits (p<0.05). In females Arg/Gln genotype showed association with stage of the disease (p=0.04). This is the first report in South Indian scenario where Arg399Gln genotypes were found to be associated with stage of the disease in females.
  
  
  CONCLUSIONS
  It is concluded that XRCC1 genotypes Gln/Gln and Arg/Gln may influence cancer susceptibility in patients with smoking habits and these functional SNPs in XRCC1 gene may act as attractive candidate biomarkers in lung cancer for diagnosis and prognosis.
authors.affiliation: Genetics Department, Bhagwan Mahavir Medical Research Centre, Masab tank, India E-mail : kaiser.jamil@gmail.com.
authors.forename: Kirmani
authors.initials: K
authors.lastname: Natukula
authors.forename: Kaiser
authors.initials: K
authors.lastname: Jamil
authors.forename: Usha Rani
authors.initials: UR
authors.lastname: Pingali
authors.forename: Venkata Satya Suresh
authors.initials: VS
authors.lastname: Attili
authors.forename: Umamaheshwar Rao Naidu
authors.initials: UR
authors.lastname: Madireddy
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D001120:Arginine / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D003062:Codon / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007194:India; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D003062:Codon; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D005973:Glutamine; D004247:DNA; D001120:Arginine