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Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy.

ABSTRACT: BACKGROUND:Adjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-based adjuvant chemotherapy (PAC). METHODS:The analysis included 572 patients, for whom six SNPs of NER genes [i.e., XPC (rs1870134 and rs2228001), ERCC2/XPD rs238406 and ERCC5/XPG (rs2094258, rs2296147 and rs873601)] were detected with the TaqMan assay. Kaplan-Meier analyses and Cox proportional hazards models were used to evaluate their associations with disease free survival (DFS) and OS of these ESCC patients receiving PAC. Receiving operating characteristic curve analysis was used to evaluate the role of the risk genotypes in the DFS and OS. RESULTS:We found that ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406 SNPs were independently associated with poorer DFS and OS of ESCC patients [ERCC5/XPG rs2094258: CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68 and P = 0.012 for DFS; adjHR = 1.99 and P = 0.0001 for OS; ERCC5/XPG rs873601: GA+GG vs. AA: adjHR = 1.59 and P = 0.024 for DFS; adjHR = 1.91 and P = 0.0005 for OS; ERCC2/XPD rs238406: TT vs. GG+GT: adjHR = 1.43 and P = 0.020 for DFS; adjHR = 1.52 and P = 0.008 for OS]. These HRs increased as the number of risk genotypes increased in the combined analysis. The model combining the risk genotypes with clinical characteristics or the TNM stage system was better in predicting outcomes in ESCC patients with PAC. CONCLUSION:SNPs of ERCC2/XPD and ERCC5/XPG may independently and jointly predict survival of ESCC patients treated with PAC in this study population. Further validation in other study populations is warranted.

SUBMITTER: Zhou F

PROVIDER: S-EPMC4888614 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy.

Zhou Fei F Zhu Meiling M Wang Mengyun M Qiu Lixin L Cheng Lei L Jia Ming M Xiang Jiaqing J Wei Qingyi Q

Journal of translational medicine 20160531 1

<h4>Background</h4>Adjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Nucleotide excision repair (NER) removes DNA-adducts in tumor cells induced by the platinum-based chemotherapy and thus may modulate efficacy of the treatment. The present study evaluated if single nucleotide polymorphisms (SNPs) of NER genes were prognostic biomarkers in ESCC patients treated with platinum-base ...[more]

PMID: 27246611

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Project description:PurposeThe degree of benefit from palliative chemotherapy differs widely among patients with metastatic esophageal squamous cell carcinoma (MESCC). The purpose of this study was to develop and validate a prognostic nomogram to predict survival and aid physicians and patients in the decision-making process regarding treatment options.Materials and methodsClinicopathologic variables and treatment outcomes of 239 patients who were diagnosed with MESCC and received either fluorouracil/cisplatin (FP) or capecitabine/cisplatin (XP) as first-line chemotherapy were reviewed. A nomogram was developed as a prognostic scoring system incorporating significant clinical and laboratory variables based on a multivariate Cox proportional hazards regression model. An independent series of 61 MESCC patients treated with FP served as an independent data set for nomogram validation.ResultsNo difference in response rate was observed between the FP group (44.8%) and the XP group (54.2%). Similarly, no significant differences in median progression-free survival and median overall survival were observed between regimen groups. Multivariate analysis showed that poor performance status (Eastern Cooperative Oncology Group [ECOG] status≥2), weight loss (10% of the weight loss for 3 months), low albumin level (≤3.5 g/dL), and absence of previous esophagectomy at the time of chemotherapy were significantly associated with low OS in both groups (p<0.05). Based on these findings, patients were classified into favorable (score, 0 to 90), intermediate (91-134), and poor (>135) prognostic groups. The median survival for those with a favorable ECOG was 13.8 months (95% confidence interval [CI], 10.8 to 18.6 months), for intermediate 11.2 months (95% CI, 8.7 to 11.9 months), and for poor, 7.0 months (95% CI, 3.6 to 10.0 months). External validation of the nomogram in a different patient cohort yielded significantly similar findings.ConclusionThe nomogram described here predicts survival in MESCC patients and could serve as a guide for the use of FP/XP chemotherapy in MESCC patients.

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Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy.

Publications

Genetic variants of DNA repair genes predict the survival of patients with esophageal squamous cell cancer receiving platinum-based adjuvant chemotherapy.

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