1. ERCC1 C8092A (rs3212986) polymorphism as a predictive marker in esophageal cancer patients treated with cisplatin/5-FU-based neoadjuvant therapy
- Author
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Francesco Cavallin, Carlo Castoro, Ermanno Ancona, Daniela Basso, Daniela Saggioro, Alberto Ruol, Rita Alfieri, Enrica Rumiato, Alberto Amadori, Elisa Boldrin, and Matteo Cagol
- Subjects
Oncology ,Adult ,Genetic Markers ,Male ,medicine.medical_specialty ,Esophageal Neoplasms ,Genotype ,medicine.medical_treatment ,Esophageal cancer ,Adenocarcinoma ,Internal medicine ,Genetics ,Carcinoma ,Medicine ,Humans ,5-fluorouracil ,Molecular Targeted Therapy ,General Pharmacology, Toxicology and Pharmaceutics ,ERCC1 polymorphism ,Molecular Biology ,Genetics (clinical) ,Neoadjuvant therapy ,Aged ,Glutathione Transferase ,Xeroderma Pigmentosum Group D Protein ,Cisplatin ,Chemotherapy ,Predictive marker ,Polymorphism, Genetic ,business.industry ,Thymidylate Synthase ,Middle Aged ,medicine.disease ,Endonucleases ,Neoadjuvant Therapy ,DNA-Binding Proteins ,Treatment Outcome ,Glutathione S-Transferase pi ,Carcinoma, Squamous Cell ,Molecular Medicine ,Female ,Fluorouracil ,ERCC1 ,business ,medicine.drug - Abstract
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.
- Published
- 2013