title: XRCC1 gene polymorphism for prediction of response and prognosis in the multimodality therapy of patients with locally advanced rectal cancer.
abstract: BACKGROUND
  Neoadjuvant treatment strategies have been developed to improve survival of patients with locally advanced rectal cancer. Since mainly patients with major histopathologic response benefit from this therapy, predictive markers are needed. The gene polymorphism of the X-ray-repair-cross complementing (XRCC1-) gene (rs25487) was analyzed to predict response to neoadjuvant radiochemotherapy and prognosis in patients with locally advanced rectal cancer.
  
  
  METHODS
  81 patients (51 male; 30 female; median age 59 years) with locally advanced rectal cancer were included in this study. All patients received a neoadjuvant radiochemotherapy (50.4 Gy, 5-FU) followed by surgical therapy. Histomorphologic regression was defined as major response when resected specimens contained less than 10% viable tumor cells (n = 28) and minor response when more than 10% viable tumor cells (n = 53) were detected in the surgical specimen. Genomic DNA was extracted from paraffin-embedded tissues of all study patients. Allelic discrimination was performed by real-time polymerase chain reaction. Two allele-specific TaqMan probes in competition were used for amplification of the XRCC1 gene. Allelic genotyping was correlated with therapy response and prognosis.
  
  
  RESULTS
  Single-nucleotide polymorphism XRCC1 A399G (rs25487) was predictive for therapy response (P = 0.039). Within the AG genotype group, 17 (53%) patients showed a minor response and 15 (47%) patients a major response. In contrast, 39 (78%) of the patients with homogeneous AA or GG genotype were minor responders and only 11 (22%) major responders. No prognostic value was revealed for the XRCC1 A399G (rs25487) gene polymorphism in the multimodality therapy.
  
  
  CONCLUSIONS
  Our data supports the role of XRCC1 as a predictive marker for therapy response in the multimodality therapy of patients with locally advanced rectal cancer. Single-nucleotide polymorphism XRCC1 A399G (rs25487) could be applied to individualize treatment strategies.
authors.affiliation: Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Grimminger
authors.forename: Jan
authors.initials: J
authors.lastname: Brabender
authors.forename: Ute
authors.initials: U
authors.lastname: Warnecke-Eberz
authors.forename: Kosuke
authors.initials: K
authors.lastname: Narumiya
authors.forename: Christoph
authors.initials: C
authors.lastname: Wandhöfer
authors.forename: Uta
authors.initials: U
authors.lastname: Drebber
authors.forename: Elfriede
authors.initials: E
authors.lastname: Bollschweiler
authors.forename: Arnulf H
authors.initials: AH
authors.lastname: Hölscher
authors.forename: Ralf
authors.initials: R
authors.lastname: Metzger
authors.forename: Daniel
authors.initials: D
authors.lastname: Vallböhmer
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000235:genetics* / Q000401:mortality / Q000628:therapy*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human