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Using Whole-Exome S...
Using Whole-Exome Sequencing to Identify Genetic Markers for Carboplatin and Gemcitabine-Induced Toxicities
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- Green, Henrik (författare)
- KTH,Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Division of Gene Technology, Royal Institute of Technology, Solna, Sweden/ Royal Institute Technology, Sweden; National Board Forens Med, Department Forens Genet and Forens Toxicol, Linkoping, Sweden,Genteknologi,Science for Life Laboratory, SciLifeLab,Linköping University, Sweden; National Board of Forensic Medicine, Sweden
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- Hasmats, Johanna (författare)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Royal Institute Technology, Sweden
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- Kupershmidt, Ilya (författare)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Royal Institute Technology, Sweden; NextBio, CA USA
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- Edsgärd, Daniel (författare)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Royal Institute Technology, Sweden
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- de Petris, Luigi (författare)
- Karolinska Institutet,Karolinska Institute, Sweden; Karolinska University Hospital, Sweden
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- Lewensohn, Rolf (författare)
- Karolinska Institutet,Karolinska Institute, Sweden; Karolinska University Hospital, Sweden
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- Blackhall, Fiona (författare)
- Christie Hospital, England; University of Manchester, England
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- Vikingsson, Svante (författare)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten
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- Besse, Benjamin (författare)
- University of Paris 11, France
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- Lindgren, Andrea (författare)
- Linköpings universitet,Institutionen för medicin och hälsa,Medicinska fakulteten,Region Östergötland, Fysiologiska kliniken US,Region Östergötland, Lungmedicinska kliniken US
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- Branden, Eva (författare)
- Karolinska Institute, Sweden; Karolinska University Hospital, Sweden
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- Koyi, Hirsh (författare)
- Karolinska Institutet,Karolinska Institute, Sweden; Karolinska University Hospital, Sweden
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- Peterson, Curt (författare)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US
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- Lundeberg, Joakim (författare)
- KTH,Genteknologi,Science for Life Laboratory, SciLifeLab,Royal Institute Technology, Sweden
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(creator_code:org_t)
- AMER ASSOC CANCER RESEARCH, 2016
- 2016
- Engelska.
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Ingår i: Clinical Cancer Research. - : AMER ASSOC CANCER RESEARCH. - 1078-0432 .- 1557-3265. ; 22:2, s. 366-373
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- Purpose: Chemotherapies are associated with significant interindividual variability in therapeutic effect and adverse drug reactions. In lung cancer, the use of gemcitabine and carboplatin induces grade 3 or 4 myelosuppression in about a quarter of the patients, while an equal fraction of patients is basically unaffected in terms of myelosuppressive side effects. We therefore set out to identify genetic markers for gemcitabine/carboplatin-induced myelosuppression. Experimental Design: We exome sequenced 32 patients that suffered extremely high neutropenia and thrombocytopenia (grade 3 or 4 after first chemotherapy cycle) or were virtually unaffected (grade 0 or 1). The genetic differences/polymorphism between the groups were compared using six different bioinformatics strategies: (i) whole-exome nonsynonymous single-nucleotide variants association analysis, (ii) deviation from Hardy-Weinberg equilibrium, (iii) analysis of genes selected by a priori biologic knowledge, (iv) analysis of genes selected from gene expression meta-analysis of toxicity datasets, (v) Ingenuity Pathway Analysis, and (vi) FunCoup network enrichment analysis. Results: A total of 53 genetic variants that differed among these groups were validated in an additional 291 patients and were correlated to the patients myelosuppression. In the validation, we identified rs1453542 in OR4D6 (P = 0.0008; OR, 5.2; 95% CI, 1.8-18) as a marker for gemcitabine/carboplatin-induced neutropenia and rs5925720 in DDX53 (P = 0.0015; OR, 0.36; 95% CI, 0.17-0.71) as a marker for thrombocytopenia. Patients homozygous for the minor allele of rs1453542 had a higher risk of neutropenia, and for rs5925720 the minor allele was associated with a lower risk for thrombocytopenia. Conclusions: We have identified two new genetic markers with the potential to predict myelosuppression induced by gemcitabine/ carboplatin chemotherapy. (C)2015 AACR.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Green, Henrik
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Hasmats, Johanna
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Kupershmidt, Ily ...
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Edsgärd, Daniel
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de Petris, Luigi
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Lewensohn, Rolf
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visa fler...
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Blackhall, Fiona
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Vikingsson, Svan ...
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Besse, Benjamin
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Lindgren, Andrea
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Branden, Eva
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Koyi, Hirsh
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Peterson, Curt
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Lundeberg, Joaki ...
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- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Medicinska och f ...
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och Medicinsk geneti ...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Clinical Cancer ...
- Av lärosätet
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Linköpings universitet
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Kungliga Tekniska Högskolan
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Karolinska Institutet