Background: DNA repair gene polymorphisms could alter DNA repair capacity and therefore associate with tumor sensitivity to radiochemotherapy. This study assessed excision repair cross-complementing group 1 (ERCC1) C118T and X-ray cross-complementing group 1 (XRCC1) G399A single-nucleotide polymorphisms in esophageal patients for an association with sensitivity to radiation and chemotherapy.
Methods: Esophageal squamous cell carcinoma patients (n = 118) who relapsed after surgery were enrolled for assessment of ERCC1 C118T and XRCC1 G399A polymorphisms by direct DNA sequencing.
Results: The response rate of treatments was 48.30%: 14 complete response (CR, 11.86%), 43 partial response (PR, 36.44%), 49 stable disease (SD, 41.53%), and 12 progressive disease (PD, 10.17%). ERCC1 C118T was significantly associated with treatment response (C/T vs. C/C + T/T, odds ratio [OR] = 6.035, 95% confidence interval [CI]: 2.114-17.226, P = 0.001) after adjusting for other clinicopathological factors. Patients carrying the C/T genotype had significantly prolonged overall survival (OS) compared with C/C and T/T (median OS 43.00 vs. 27.00, P = 0.027). Multivariate Cox regression showed that a response was only an independent prognostic factor for OS (CR + PR vs. SD+PD, HR = 0.471 95% CI 0.269-0.826, P = 0.009). Grade III and IV adverse events occurred in 12 of 118 patients (10.17%). Only concurrent radiochemotherapy significantly increased these adverse events (OR = 26.529, 95% CI 2.312-304.389, P = 0.008).
Conclusion: ERCC1 C118T could be a predictive factor for the response to radiotherapy and chemotherapy, but not a prognostic factor for OS in esophageal cancer patients after surgery.
Keywords: ERCC1; Esophageal carcinoma; XRCC1; radiochemotherapy; single nucleotide polymorphism.