title: The XRCC1 codon 399 Gln allele is associated with adenine to guanine p53 mutations in non-small cell lung cancer.
abstract: The X-ray repair cross-complementing group 1 (XRCC1) gene plays a critical role in the repair of DNA single-strand breaks. A polymorphism at codon 399 of the XRCC1 gene (Arg to Gln) is associated with increased DNA adduct binding and an increase in sister chromatid exchanges after exposure to tobacco carcinogens and may be linked with an increased risk of lung cancer. To further define the interaction between tobacco carcinogens, XRCC1-mediated DNA repair and DNA damage, we examined the role of the XRCC1 codon 399 polymorphism in mutation of the p53 gene in non-small cell lung cancer (NSCLC). Tumor and non-neoplastic (lung or lymphocyte) samples were collected from 116 cigarette smokers with NSCLC. p53 mutations were detected by direct sequencing and/or the GeneChip p53 assay in 63 of 116 (54%) tumors. XRCC1 polymorphisms were identified by PCR/RFLP analysis. The distribution of XRCC1 codon 399 genotypes was (Arg/Arg [74 of 116, 64%], Arg/Gln [29 of 116, 25%], and Gln/Gln [13 of 116, 11%]). The prevalence of p53 mutations was similar among subjects with all three XRCC1 genotypes (Arg/Arg [39 of 74, 53%], Arg/Gln [18 of 29, 62%], and Gln/Gln [6 of 13, 46%]). However, the prevalence of specific p53 mutations varied among different XRCC1 genotypes. AT to GC transitions were significantly (P=0.01) more common among subjects with the Gln/Arg or Gln/Gln genotype (5 of 42, 12%) than in subjects with the Arg/Arg genotype (1 of 74, 1.4%). In summary, the XRCC1 Gln allele is associated with AT to GC mutations in p53 in NSCLC. The XRCC1 gene may play a role in the repair of cigarette smoking-induced DNA damage.
authors.affiliation: Department of Surgery, Box SURG, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14642, USA.
authors.forename: Celine
authors.initials: C
authors.lastname: Casse
authors.forename: Ying Chuan
authors.initials: YC
authors.lastname: Hu
authors.forename: Steven A
authors.initials: SA
authors.lastname: Ahrendt
mesh_terms: D000225:Adenine; D000483:Alleles; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D004268:DNA-Binding Proteins; D005260:Female; D016158:Genes, p53; D005838:Genotype; D006147:Guanine; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012907:Smoking / Q000009:adverse effects; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D006147:Guanine; D000225:Adenine