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Identification of candidate SNPs for drug induced toxicity from differentially expressed genes in associated tissues
Royal Institute Technology, Sweden .
NextBio, CA 95050 USA Royal Institute Technology, Sweden .
Spanish National Cancer Centre CNIO, Spain .
NextBio, CA 95050 USA .
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2012 (English)In: Gene, ISSN 0378-1119, E-ISSN 1879-0038, Vol. 506, no 1, 62-68 p.Article in journal (Refereed) Published
Abstract [en]

The growing collection of publicly available high-throughput data provides an invaluable resource for generating preliminary in silico data in support of novel hypotheses. In this study we used a cross-dataset meta-analysis strategy to identify novel candidate genes and genetic variations relevant to paclitaxel/carboplatin-induced myelosuppression and neuropathy. We identified genes affected by drug exposure and present in tissues associated with toxicity. From ten top-ranked genes 42 non-synonymous single nucleotide polymorphisms (SNPs) were identified in silico and genotyped in 94 cancer patients treated with carboplatin/paclitaxel. We observed variations in 11 SNPs, of which seven were present in a sufficient frequency for statistical evaluation. Of these seven SNPs. three were present in ABCA1 and ATM, and showed significant or borderline significant association with either myelosuppression or neuropathy. The strikingly high number of associations between genotype and clinically observed toxicity provides support for our data-driven computations strategy to identify biomarkers for drug toxicity.

Place, publisher, year, edition, pages
Elsevier , 2012. Vol. 506, no 1, 62-68 p.
Keyword [en]
Paclitaxel, Carboplatin, Single nucleotide polymorphism, Toxicity, Gene expression microarrays, Meta-analysis
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-84332DOI: 10.1016/j.gene.2012.06.053ISI: 000308260400010OAI: diva2:558926

Funding Agencies|European Commission|CHEMORES LSHC-CT-2007-037665|Swedish Cancer Society||Swedish Research Council||Swedish Cancer Foundation||County Council in Ostergotland||

Available from: 2012-10-05 Created: 2012-10-05 Last updated: 2014-01-22Bibliographically approved

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Suleman Khan, MuhammadGreen, Henrik
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Division of Drug ResearchFaculty of Health SciencesClinical Pharmacology
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ReferencesLink to record
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