Dataset Information

DNA repair gene ERCC1 C118T polymorphism predicts sensitivity of recurrent esophageal cancer to radiochemotherapy in a Chinese population.

ABSTRACT:

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.

SUBMITTER: Yu X

PROVIDER: S-EPMC4632926 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundExcision repair cross-complementing group 1 (ERCC1) was considered a potential candidate gene for ischemic stroke, and its polymorphisms might be associated with the susceptibility to ischemic stroke.MethodsA total of 513 patients with ischemic stroke and 550 control subjects were recruited. The expression levels of ERCC1 messenger RNA (mRNA) in peripheral blood mononuclear cells and its protein in plasma were detected by quantitative real-time PCR (qPCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Rs3212986 polymorphism of ERCC1 was detected by PCR-restriction fragment length polymorphism (RFLP-PCR) and was confirmed by sequencing. The association between the ERCC1 rs3212986 polymorphism or its expression and ischemic stroke was further analyzed.ResultsThe ERCC1 mRNA level in patients with ischemic stroke was lower than that in the control group (P < 0.05). However, the ERCC1 protein level in patients with ischemic stroke was higher than that in the control group (P < 0.05). The A allele of rs3212986 was associated with increased ischemic stroke risk (OR = 1.287, 95% CI = 1.076-1.540, P = 0.006). The association between rs3212986 polymorphism and ischemic stroke susceptibility was found in both recessive (OR = 2.638, 95% CI = 1.744-3.989, P < 0.001) and additive models (OR = 1.309, 95% CI = 1.028-1.667, P = 0.031), respectively. Similar results were obtained in the recessive model (OR = 2.015, 95% CI = 1.087-3.704, P = 0.026) after adjusting for demographic information and other variables. Additionally, the level of ERCC1 mRNA in the CC/CA genotype was higher than that in the AA genotype (P < 0.05).ConclusionIt was suggested that the ERCC1 rs3212986 polymorphism was associated with ischemic stroke susceptibility in a Chinese Han population and that an A allele of rs3212986 was related to increased ischemic stroke risk. The altered ERCC1 expression level caused by the rs3212986 polymorphism might participate in the pathophysiological process of ischemic stroke.