Explorative study to identify novel candidate genes related to oxaliplatin efficacy and toxicity using a DNA repair array
| Autor: | Henk-Jan Guchelaar, Ninja Antonini, Cornelis J. A. Punt, Hans Gelderblom, D. M. Kweekel, J.W.R. Nortier |
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| Přispěvatelé: | Other departments |
| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Candidate gene DNA Repair Organoplatinum Compounds DNA repair efficacy Single-nucleotide polymorphism Cell Cycle Proteins Ataxia Telangiectasia Mutated Proteins Biology Protein Serine-Threonine Kinases Bioinformatics Deoxycytidine Polymorphism Single Nucleotide Immune Regulation [NCMLS 2] Translational research [ONCOL 3] Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Genotyping Capecitabine Hereditary cancer and cancer-related syndromes [ONCOL 1] Tumor Suppressor Proteins oxaliplatin toxicity Nuclear Proteins Genetics and Genomics Endonucleases Oxaliplatin Minor allele frequency DNA-Binding Proteins ATM Fluorouracil SNP array Nucleotide excision repair medicine.drug ERCC5 Transcription Factors |
| Zdroj: | British Journal of Cancer British journal of cancer, 101(2), 357-362. Nature Publishing Group British Journal of Cancer, 101, 2, pp. 357-62 British Journal of Cancer, 101, 357-62 |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Item does not contain fulltext PURPOSE: To identify new polymorphisms (single nucleotide polymorphisms, SNPs) in DNA repair pathways that are associated with efficacy and toxicity in patients receiving oxaliplatin and capecitabine for advanced colorectal cancer (ACC). METHODS: We studied progression-free survival (PFS) in 91 ACC patients, of whom germ-line DNA was isolated and genotyped using an Asper Biotech array. Overall survival (OS) and toxicity were studied as secondary end points. A step-wise selection of SNPs was performed, involving univariate and multivariate log-rank tests and Cox regression analysis, with age and performance status as covariates. RESULTS: A total of 81 SNPs in 46 genes on the array were selected for further analysis, based on genotyping success rates and minor allele frequencies. After step-wise selection, we found that homozygosity for the ataxia telangiectasia mutated gene (ATM) rs1801516 or excision repair cross-complementing gene (ERCC5) rs1047768 SNPs was associated with shorter PFS; however there were no significant associations (P>0.01) with OS or toxicity. DISCUSSION: This is the first study describing the pathway gene approach for the selection of new candidate genes involved in oxaliplatin efficacy and toxicity. The results suggest that the ATM and ERCC5 genes may be associated with oxaliplatin efficacy in ACC. |
| Databáze: | OpenAIRE |
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