Genetic variability of the ABCC2 gene and clinical outcomes in pancreatic cancer patients
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
30629142
DOI
10.1093/carcin/bgz006
PII: 5281404
Knihovny.cz E-resources
- MeSH
- Carcinoma, Pancreatic Ductal genetics mortality pathology therapy MeSH
- Genotype MeSH
- Polymorphism, Single Nucleotide * MeSH
- Combined Modality Therapy MeSH
- Middle Aged MeSH
- Humans MeSH
- Survival Rate MeSH
- Biomarkers, Tumor genetics MeSH
- Pancreatic Neoplasms genetics mortality pathology therapy MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Multidrug Resistance-Associated Protein 2 MeSH
- Multidrug Resistance-Associated Proteins genetics MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- ABCC2 protein, human MeSH Browser
- Biomarkers, Tumor MeSH
- Multidrug Resistance-Associated Protein 2 MeSH
- Multidrug Resistance-Associated Proteins MeSH
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis, caused by various factors, such as the aggressiveness of the disease, the limited therapeutic options and the lack of early detection and risk markers. The ATP binding cassette subfamily C member 2 (ABCC2) protein plays a critical role in response to various drugs and is differentially expressed in gemcitabine sensitive and resistant cells. Moreover, single nucleotide polymorphisms (SNPs) in the gene have been associated with differential outcomes and prognosis in several tumour types. The aim of this study was to investigate the possible association between SNPs in the ABCC2 gene and overall survival (OS) in PDAC patients. We analysed 12 polymorphisms, including tagging-SNPs covering all the genetic variability of the ABCC2 gene and genotyped them in 1415 PDAC patients collected within the Pancreatic Disease ReseArch (PANDoRA) consortium. We tested the association between ABCC2 SNPs and PDAC OS using Cox proportional hazard models. We analysed PDAC patients dividing them by stage and observed that the minor alleles of three SNPs showed an association with worse OS [rs3740067: hazard ratio (HR) = 3.29, 95% confidence interval (CI) = 1.56-6.97, P = 0.002; rs3740073: HR = 3.11, 95% CI = 1.52-6.38, P = 0.002 and rs717620: HR = 2.90, 95% CI = 1.41-5.95, P = 0.004, respectively] in stage I patients. In patients with more advanced PDAC, we did not observe any statistically significant association. Our results suggest that rs3740067, rs3740073 and rs717620 could be promising prognostic markers in stage I PDAC patients.
1st Department of Medicine University of Szeged Szeged Hungary
ARC Net Research Centre University Hospital G B Rossi University of Verona Verona Italy
Biomedical Center Faculty of Medicine in Pilsen Charles University Pilsen Czech Republic
Department of Biology University of Pisa Pisa Italy
Department of Digestive Tract Diseases Medical University of Lodz Lodz Poland
Department of Surgery Gastroenterology and Oncology University of Padua Padua Italy
Digestive and Liver Disease Unit S Andrea Hospital Rome Italy
Genomic Epidemiology Group German Cancer Research Center Heidelberg Germany
Institute for Translational Medicine University of Pécs Pécs Hungary
János Szentágothai Research Centre and Centre for Neuroscience University of Pécs Pécs Hungary
Pancreas Unit Department of Digestive System Sant'Orsola Malpighi Hospital Bologna Italy
References provided by Crossref.org
Protein expression of ABCC2 and SLC22A3 associates with prognosis of pancreatic adenocarcinoma
