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  • Björn, NiclasLinköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Linköping Univ, Dept Biomed & Clin Sci, Div Clin Chem & Pharmacol, Linköping, Sweden (author)

The association of four genetic variants with myelosuppression in gemcitabine-treated Japanese is not evident in gemcitabine/carboplatin-treated Swedes

  • Article/chapterEnglish2022

Publisher, publication year, extent ...

  • 2022-02-14
  • John Wiley & Sons,2022
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:oru-97778
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-97778URI
  • https://doi.org/10.1111/bcpt.13712DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-183220URI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-485712URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:148816772URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding agencies:ALF grants Region ÖstergötlandFunds of RadiumhemmetMarcus Borgströms stiftelse
  • Funding Agencies|Swedish Cancer SocietySwedish Cancer Society; Swedish Research CouncilSwedish Research CouncilEuropean Commission; Linkoping University; ALF grants Region ostergotland; Funds of Radiumhemmet; Marcus Borgstroms stiftelse
  • 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.

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  • Jakobsen Falk, Ingrid,1984-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(Swepub:liu)ingja10 (author)
  • Udagawa, ChihiroDepartment of Genetic Medicine and Services, National Cancer Center Hospital, Tokyo, Japan,Natl Canc Ctr, Dept Genet Med & Serv, Tokyo, Japan (author)
  • Brandén, EvaUppsala universitet,Centrum för klinisk forskning, Gävleborg,Gävle Cent Hosp, Dept Resp Med, Gävle, Sweden(Swepub:uu)evabr789 (author)
  • Koyi, HirshKarolinska Institutet,Uppsala universitet,Centrum för klinisk forskning, Gävleborg,Gävle Cent Hosp, Dept Resp Med, Gävle, Sweden(Swepub:uu)hirko843 (author)
  • Lewensohn, RolfKarolinska Institutet (author)
  • De Petris, LuigiKarolinska Institutet (author)
  • Zembutsu, HitoshiDepartment of Clinical Genomics, National Cancer Center Research Institute, Tokyo, Japan,Natl Canc Ctr, Res Inst, Dept Clin Genom, Tokyo, Japan (author)
  • Green, HenrikLinköpings 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(Swepub:liu)hengr89 (author)
  • Linköpings universitetAvdelningen för klinisk kemi och farmakologi (creator_code:org_t)

Related titles

  • In:Basic & Clinical Pharmacology & Toxicology: John Wiley & Sons130:4, s. 513-5211742-78351742-7843

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