Association of single nucleotide polymorphisms in XRCC1 and ATM with recurrence in patients with cervical cancer

ObjectiveThe primary objective of this study was to determine the association of the genotype of X-ray repair complementing defective repair in Chinese hamster cell 1 (XRCC1) 580C>T with recurrence-free survival (RFS) in patients with cervical cancer who underwent radical surgery followed by adjuvant concurrent chemoradiation (CRT). Secondary objectives were to assess 1) the association of single nucleotide polymorphisms (SNPs) in XRCC1 and ataxia telangiectasia mutated (ATM) gene with RFS, overall survival (OS) and completion of CRT, 2) the association of haplotypes of XRCC1 and ATM with RFS, OS and completion of CRT, 3) concordance rate between genotypes from cancer tissue and that from normal tissue and 4) the association of clinicopathologic variables with RFS and OS. Materials and MethodsClinicopathologic variables were extracted from medical records of 159 patients who underwent radical hysterectomy followed by adjuvant CRT in a cancer center between 1999 and 2004. After exclusion of six patients without paraffin blocks, 153 patients were included in this study. DNA was extracted from a formalin-fixed, paraffin embedded tissue block containing tumor tissue and another block containing uninvolved lymph node. Genotyping for XRCC1 580C>T (rs 1799782), XRCC1 1196A>G (rs 25487), ATM 3078-77C>T (rs 664677), ATM 5557G>A (rs 1801516) and ATM 6807+238G>C (rs609429) was performed using pyrosequencing. Haplotype estimation was performed using haplo.stats in R version 2.15.0. The association of genotype or haplotype of SNPs with RFS, OS and completion of CRT was evaluated via Cox regression analysis, chi-square or Fishers exact test. The concordance rate between genotype from cancer tissue and that from normal tissue was examined according to SNP. The association of clinicopathologic variables with RFS and OS was estimated via Cox regression analysis. ResultsNone of SNPs was associated with RFS, OS and completion of CRT. Concordance rate between genotype from cancer tissue and that from normal tissue for XRCC1 580C>T, XRCC1 1196A>G, ATM 3078-77C>T, ATM 5557G>A and ATM 6807+238G>C were 72%, 88%, 73%, 100% and 54%, respectively. Age, stage, histologic type, LVSI and parametrial invasion were associated with RFS, and clinical tumor size, resection margin, lymph node involvement and completion of CRT were associated with OS. ConclusionGenotype of XRCC1 580C>T was not associated with RFS in patients with cervical cancer who underwent radical surgery followed by adjuvant CRT. Low concordance rate between cancer and germline genotype was identified in cervical cancer.