Abstract
BackgroundAdjuvant 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).MethodsThe 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.ResultsWe 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.ConclusionSNPs 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12967-016-0903-z) contains supplementary material, which is available to authorized users.
Highlights
Adjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS)
In the multivariate analyses with adjustment for all the variables listed in Table 1, we found that disease free survival (DFS) of the patients was significantly associated with ERCC5/XPG rs2094258 (CT+TT vs. CC: adjusted hazards ratio (adjHR) = 1.68, 95 % confidence interval (CI) 1.23–2.31, and P = 0.012), rs873601 (GG+GA vs. AA: adjHR = 1.59, 95 % CI 1.06–2.37, and P = 0.024), and ERCC2/XPD rs238406 (TT vs. GG+GT: adjHR = 1.43, 95 % CI 1.06–1.93, and P = 0.020) (Table 2)
In this study, we reported that some single nucleotide polymorphism (SNP) of the Nucleotide excision repair (NER) genes, such as ERCC5/XPG rs2094258 and rs873601 and ERCC2/XPD rs238406, may independently or jointly influence the prognosis of ESCC patients treated with platinum-based adjuvant chemotherapy (PAC) in eastern China
Summary
Adjuvant chemotherapy in patients with resected esophageal squamous cell cancer (ESCC) remains controversial for its uncertain role in improving overall survival (OS). Surgery remains the standard treatment for resectable ESCC in China. For those patients who received an esophagectomy alone, their 5-year survival is still in a disappointing range of 15–40 % [2]. The results of some major multicenter prospective randomized controlled trials (MPRCTs) were controversial. Most of these trials were conducted in western countries, and more than 50 % of the patients included in these trials were diagnosed with an adenocarcinoma. Of the four MPRCTs employing neoadjuvant chemotherapy, two reported benefits in OS [8, 9] but the other two did not [10, 11]
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