aImmunology and Molecular Oncology Unit bOncological Surgery Unit, Veneto Institute of Oncology IOV-IRCCS Departments of cLaboratory Medicine dSurgical Sciences, Oncology and Gastroenterology, University of Padova, Padova, Italy.
Pharmacogenet Genomics. 2013 Nov;23(11):597-604. doi: 10.1097/FPC.0b013e3283653afc.
At present, no consensus exists on the beneficial effect of preoperative cisplatin/5-fluorouracil (5-FU)-based chemotherapy versus primary surgery in the management of patients with esophageal cancer. The aim of this study was to evaluate the impact of some relevant genetic polymorphisms, within drug-related and DNA repair genes, on the clinical outcome of esophageal cancer patients subjected to cisplatin/5-FU-based neoadjuvant treatment.
DNA from 143 esophageal cancer patients, 63 receiving neoadjuvant therapy and 80 receiving primary surgery, was analyzed for the following polymorphisms: the GSTM1 null, GSTT1 null, and GSTP1 Ile105Val (rs16953) in glutathione S-transferase (GST) family, 2 in thymidylate synthase (TS) gene, and the ERCC1 Asn118Asn (rs11615), ERCC1 C8092A (rs3212986), XPD/ERCC2 Asp312Asn (rs1799793), and XPD/ERCC2 Lys751Gln (rs13181) of the nucleotide excision repair pathway.
We found that the ERCC1 rs3212986, although not associated with therapeutic response, is an independent predictive marker of better outcome in a cisplatin/5-FU-based neoadjuvant setting (hazard ratio: 0.38, 95% confidence interval: 0.2-0.73, P=0.008). In contrast, no association with clinical outcome was observed for this polymorphism in the primary surgery group.
Our study indicates the ERCC1 rs3212986 as a predictive marker in the cisplatin/5-FU-based neoadjuvant setting, and also suggests its use as a marker to select the appropriate therapeutic approach in esophageal cancer patients.
目前，对于接受顺铂/5-氟尿嘧啶（5-FU）为基础的化疗与初次手术治疗食管癌患者的获益效果，尚无共识。本研究旨在评估药物相关和 DNA 修复基因中一些相关遗传多态性对接受顺铂/5-FU 为基础新辅助治疗的食管癌患者临床结局的影响。
对 143 例食管癌患者的 DNA 进行分析，其中 63 例接受新辅助治疗，80 例接受初次手术。分析了谷胱甘肽 S-转移酶（GST）家族中的 GSTM1 缺失、GSTT1 缺失和 GSTP1 Ile105Val（rs16953）、胸苷酸合成酶（TS）基因中的 2 个基因以及核苷酸切除修复途径中的 ERCC1 Asn118Asn（rs11615）、ERCC1 C8092A（rs3212986）、XPD/ERCC2 Asp312Asn（rs1799793）和 XPD/ERCC2 Lys751Gln（rs13181）多态性。
我们发现，虽然 ERCC1 rs3212986 与治疗反应无关，但它是顺铂/5-FU 为基础新辅助治疗中更好结局的独立预测标志物（危险比：0.38，95%置信区间：0.2-0.73，P=0.008）。相比之下，该多态性在初次手术组中与临床结局无关。
我们的研究表明，ERCC1 rs3212986 是顺铂/5-FU 为基础新辅助治疗的预测标志物，并提示其可作为选择食管癌患者适当治疗方法的标志物。
