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The association of ...
The association of four genetic variants with myelosuppression in gemcitabine-treated Japanese is not evident in gemcitabine/carboplatin-treated Swedes
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- Björn, Niclas (author)
- Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Linköping Univ, Dept Biomed & Clin Sci, Div Clin Chem & Pharmacol, Linköping, Sweden
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- Jakobsen Falk, Ingrid, 1984- (author)
- Linköpings universitet,Örebro universitet,Institutionen för medicinska vetenskaper,Region Örebro län,Division of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Laboratory Medicine, Örebro University Hospital, Örebro, Sweden,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Linköping Univ, Dept Biomed & Clin Sci, Div Clin Chem & Pharmacol, Linköping, Sweden.;Örebro Univ Hosp, Dept Lab Med, Örebro, Sweden
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- Udagawa, Chihiro (author)
- Department of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan,Natl Canc Ctr, Dept Genet Med & Serv, Tokyo, Japan
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- Brandén, Eva (author)
- Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Gävle Cent Hosp, Dept Resp Med, Gävle, Sweden
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- Koyi, Hirsh (author)
- Karolinska Institutet,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Gävle Cent Hosp, Dept Resp Med, Gävle, Sweden
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- Lewensohn, Rolf (author)
- Karolinska Institutet
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- De Petris, Luigi (author)
- Karolinska Institutet
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- Zembutsu, Hitoshi (author)
- Department of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan,Natl Canc Ctr, Res Inst, Dept Clin Genom, Tokyo, Japan
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- Green, Henrik (author)
- Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Linköping Univ, Dept Biomed & Clin Sci, Div Clin Chem & Pharmacol, Linköping, Sweden.;Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linköping, Sweden
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(creator_code:org_t)
- 2022-02-14
- 2022
- English.
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In: Basic & Clinical Pharmacology & Toxicology. - : John Wiley & Sons. - 1742-7835 .- 1742-7843. ; 130:4, s. 513-521
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Abstract
Subject headings
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- Gemcitabine/carboplatin-induced myelosuppressive adverse drug reactions (ADRs) are clinical problems leading to patient suffering and dose alterations. There is a need for personalised medicine to improve treatment effects and patients' well-being. We tested four genetic variants, rs11141915, rs1901440, rs12046844 and rs11719165, previously suggested as potential biomarkers for gemcitabine-induced leukopenia/neutropenia in Japanese patients, in 213 Swedish gemcitabine/carboplatin-treated non-small cell lung cancer (NSCLC) patients. DNA was genotyped using TaqMan probes and real-time PCR. The relationships between the risk alleles and low toxicity (non-ADR: Common Terminology Criteria for Adverse Events [CTCAE] grades 0) or high toxicity (ADR: CTCAE grades 3-4) of platelets, leukocytes and neutrophils were evaluated using Fisher's exact test. The risk alleles did not correlate with myelosuppression, and the strongest borderline significance (not withstanding adjustment for multiple testing) was for rs1901440 (neutropenia, p = 0.043) and rs11719165 (leukopenia, p = 0.049) where the risk alleles trended towards lower toxicity, contrasting with previous study findings. Risk alleles and higher risk scores were more common among our patients. We conclude that the genetic variants do not apply to Swedish patients treated with gemcitabine/carboplatin. However, they can still be important in other populations and cohorts, especially in a gemcitabine monotherapy setting, where the causal genetic variation might influence myelosuppressive ADRs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Kardiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cardiac and Cardiovascular Systems (hsv//eng)
Keyword
- adverse drug reactions
- carboplatin
- gemcitabine
- myelosuppression
- non-small cell lung cancer
Publication and Content Type
- ref (subject category)
- art (subject category)
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