XRCC1 Gene Polymorphism for Prediction of Response and Prognosis in the Multimodality Therapy of Patients with Locally Advanced Rectal Cancer

Grimminger, Peter P.; Brabender, Jan; Warnecke-Eberz, Ute; Narumiya, Kosuke; Wandhöfer, Christoph; Drebber, Uta; Bollschweiler, Elfriede; Hölscher, Arnulf H.; Metzger, Ralf; Vallböhmer, Daniel

doi:10.1016/j.jss.2010.08.002

« Previous Next »Journal of Surgical Research
Volume 164, Issue 1 , Pages e61-e66, November 2010

XRCC1 Gene Polymorphism for Prediction of Response and Prognosis in the Multimodality Therapy of Patients with Locally Advanced Rectal Cancer

Peter P. Grimminger, M.D.
- Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany
Jan Brabender, M.D.
- Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany
Ute Warnecke-Eberz, Ph.D.
- Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany
Kosuke Narumiya, M.D.
- Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany
Christoph Wandhöfer, M.D.
- Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany
Uta Drebber, M.D.
- Department of Pathology, University of Cologne, Cologne, Germany
Elfriede Bollschweiler, M.D.
- Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany
Arnulf H. Hölscher, M.D., F.R.C.S., F.A.C.S.
- Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany
Ralf Metzger, M.D.
- Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany
Daniel Vallböhmer, M.D.
- Department of General, Visceral, and Cancer Surgery, University of Cologne, Cologne, Germany
- To whom correspondence and reprint requests should be addressed at Department of General, Visceral, and Cancer Surgery, University of Cologne, Kerpenerstrasse 62, 50937 Cologne, Germany.

Received 1 March 2010 published online 01 September 2010.

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.

Patients and 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.

Conclusion

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.

Key Words: locally advanced rectal cancer, prognostic and predictive, biomarker, XRCC1, neoadjuvant radiochemotherapy