X-ray cross-complementing group 1 and thymidylate synthase polymorphisms might predict response to chemoradiotherapy in rectal cancer patients.

Maria J Lamas, Goretti Duran, Antonio Gomez, Emilia Balboa, Urbano Anido, Beatriz Bernardez, Pablo Rana-Diez, Rafael Lopez, Angel Carracedo, Francisco Barros

Oncology Pharmacy Unit, Complejo Hospitalario Universitario of Santiago, Santiago de Compostela, Spain. mlamasd@yahoo.es

International journal of radiation oncology, biology, physics 2012 Jan 1

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5-Fluorouracil-based chemoradiotherapy before total mesorectal excision is currently the standard treatment of Stage II and III rectal cancer patients. We used known predictive pharmacogenetic biomarkers to identify the responders to preoperative chemoradiotherapy in our series. A total of 93 Stage II-III rectal cancer patients were genotyped using peripheral blood samples. The genes analyzed were X-ray cross-complementing group 1 (XRCC1), ERCC1, MTHFR, EGFR, DPYD, and TYMS. The patients were treated with 225 mg/m(2)/d continuous infusion of 5-fluorouracil concomitantly with radiotherapy (50.4 Gy) followed by total mesorectal excision. The outcomes were measured by tumor regression grade (TRG) as a major response (TRG 1 and TRG 2) or as a poor response (TRG3, TRG4, and TRG5). The major histopathologic response rate was 47.3%. XRCC1 G/G carriers had a greater probability of response than G/A carriers (odds ratio, 4.18; 95% confidence interval, 1.62-10.74, p = .003) Patients with polymorphisms associated with high expression of thymidylate synthase (2R/3G, 3C/3G, and 3G/3G) showed a greater pathologic response rate compared with carriers of low expression (odds ratio, 2.65; 95% confidence interval, 1.10-6.39, p = .02) No significant differences were seen in the response according to EGFR, ERCC1, MTHFR_C677 and MTHFR_A1298 expression. XRCC1 G/G and thymidylate synthase (2R/3G, 3C/3G, and 3G/3G) are independent factors of a major response. Germline thymidylate synthase and XRCC1 polymorphisms might be useful as predictive markers of rectal tumor response to neoadjuvant chemoradiotherapy with 5-fluorouracil. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Maria J Lamas, Goretti Duran, Antonio Gomez, Emilia Balboa, Urbano Anido, Beatriz Bernardez, Pablo Rana-Diez, Rafael Lopez, Angel Carracedo, Francisco Barros. X-ray cross-complementing group 1 and thymidylate synthase polymorphisms might predict response to chemoradiotherapy in rectal cancer patients. International journal of radiation oncology, biology, physics. 2012 Jan 1;82(1):138-44