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ERCC1 C8092A (rs3212986) polymorphism as a predictive marker in esophageal cancer patients treated with cisplatin/5-FU-based neoadjuvant therapy
- Source :
- Pharmacogenetics and genomics. 23(11)
- Publication Year :
- 2013
-
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.
- 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
Subjects
Details
- ISSN :
- 17446880
- Volume :
- 23
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Pharmacogenetics and genomics
- Accession number :
- edsair.doi.dedup.....b8116f8fb56d7756065c0b8f966433c2