XRCC1 gene polymorphism for prediction of response and prognosis in the multimodality therapy of patients with locally advanced rectal cancer.
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.
Grimminger
Peter P
PP
Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany.
Brabender
Jan
J
Warnecke-Eberz
Ute
U
Narumiya
Kosuke
K
Wandhöfer
Christoph
C
Drebber
Uta
U
Bollschweiler
Elfriede
E
Hölscher
Arnulf H
AH
Metzger
Ralf
R
Vallböhmer
Daniel
D
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
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human