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Polymorphisms in the novel serotonin receptor subunit gene HTR3C show different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy

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The aim of this study was to correlate chemotherapy-induced nausea and vomiting (CINV) with commonly occurring single nucleotide polymorphisms (SNP) in the 5-hydroxytryptamine receptor 3 genes (HTR3). Women with breast cancer without previous chemotherapy were eligible for this prospective study. All patients received epirubicin, with or without cyclophosphamide, and preventive medication with ondansetron and dexamethasone. The patients documented every vomiting event on an hourly basis. Real-time polymerase chain reaction (PCR) analysis was performed for the following nonsynonymous SNPs: p.Y129S (HTR3B), p.K163N (HTR3C) and p.A405G (HTR3C). The overall proportion of patients (total n = 110) who reported vomiting in the first 24 h after chemotherapy was 31.8%. The variant genotype of K163N (HTR3C) was associated with vomiting, which occurred in 50.0% (P = 0.009). Polymorphisms in the HTR3C gene could serve as a predictive factor for CINV in patients undergoing moderately emetogenic chemotherapy.

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  • Boyd GW, Low P, Dunlop JI, Robertson LA, Vardy A, Lambert JJ, Peters JA, Connolly CN (2002) Assembly and cell surface expression of homomeric and heteromeric 5-HT3 receptors: the role of oligomerization and chaperone proteins. Mol Cell Neurosci 21:38–50

    Article  PubMed  CAS  Google Scholar 

  • Davies PA, Pistis M, Hanna MC, Peters JA, Lambert JJ, Hales TG, Kirkness EF (1999) The 5-HT3B subunit is a major determinant of serotonin-receptor function. Nature 397:359–363

    Article  PubMed  CAS  Google Scholar 

  • del Giglio A, Soares HP, Caparroz C, Castro PC (2000) Granisetron is equivalent to ondansetron for prophylaxis of chemotherapy-induced nausea and vomiting: results of a meta-analysis of randomized controlled trials. Cancer 89:2301–2308

    Article  PubMed  Google Scholar 

  • Dubin AE, Huvar R, D’Andrea MR, Pyati J, Zhu JY, Joy KC, Wilson SJ, Galindo JE, Glass CA, Luo L, Jackson MR, Lovenberg TW, Erlander MG (1999) The pharmacological and functional characteristics of the serotonin 5-HT(3A) receptor are specifically modified by a 5-HT(3B) receptor subunit. J Biol Chem 274:30799–30810

    Article  PubMed  CAS  Google Scholar 

  • Hoyer D, Hannon JP, Martin GR (2002) Molecular, pharmacological and functional diversity of 5-HT receptors. Pharmacol Biochem Behav 71:533–554

    Article  PubMed  CAS  Google Scholar 

  • Kaiser R, Tremblay PB, Sezer O, Possinger K, Roots I, Brockmoller J (2004) Investigation of the association between 5-HT3A receptor gene polymorphisms and efficiency of antiemetic treatment with 5-HT3 receptor antagonists. Pharmacogenetics 14:271–278

    Article  PubMed  CAS  Google Scholar 

  • Karnovsky AM, Gotow LF, McKinley DD, Piechan JL, Ruble CL, Mills CJ, Schellin KA, Slightom JL, Fitzgerald LR, Benjamin CW, Roberds SL (2003) A cluster of novel serotonin receptor 3-like genes on human chromosome 3. Gene 319:137–148

    Article  PubMed  CAS  Google Scholar 

  • Kris MG, Hesketh PJ, Somerfield MR, Feyer P, Clark-Snow R, Koeller JM, Morrow GR, Chinnery LW, Chesney MJ, Gralla RJ, Grunberg SM (2006) American Society of Clinical Oncology guideline for antiemetics in oncology: update 2006. J Clin Oncol 24:2932–2947

    Article  PubMed  CAS  Google Scholar 

  • Krzywkowski K, Jensen AA, Connolly CN, Brauner-Osborne H (2007) Naturally occurring variations in the human 5-HT3A gene profoundly impact 5-HT3 receptor function and expression. Pharmacogenet Genomics 17:255–266

    Article  PubMed  CAS  Google Scholar 

  • Miyake A, Mochizuki S, Takemoto Y, Akuzawa S (1995) Molecular cloning of human 5-hydroxytryptamine3 receptor: heterogeneity in distribution and function among species. Mol Pharmacol 48:407–416

    PubMed  CAS  Google Scholar 

  • Niesler B, Frank B, Kapeller J, Rappold GA (2003) Cloning, physical mapping and expression analysis of the human 5-HT3 serotonin receptor-like genes HTR3C, HTR3D and HTR3E. Gene 310:101–111

    Article  PubMed  CAS  Google Scholar 

  • Niesler B, Walstab J, Combrink S, Moeller D, Kapeller J, Rietdorf J, Boenisch H, Goethert M, Rappold G, Bruess M (2007) Characterization of the novel human serotonin receptor subunits 5-HT3C, 5- HT3D and 5-HT3E. Mol Pharmacol 72(1):8–17

    Article  PubMed  CAS  Google Scholar 

  • Nowak AK, Wilcken NR, Stockler MR, Hamilton A, Ghersi D (2004) Systematic review of taxane-containing versus non-taxane-containing regimens for adjuvant and neoadjuvant treatment of early breast cancer. Lancet Oncol 5:372–380

    Article  PubMed  CAS  Google Scholar 

  • Reeves DC, Lummis SC (2002) The molecular basis of the structure and function of the 5-HT3 receptor: a model ligand-gated ion channel (review). Mol Membr Biol 19:11–26

    Article  PubMed  CAS  Google Scholar 

  • Tremblay PB, Kaiser R, Sezer O, Rosler N, Schelenz C, Possinger K, Roots I, Brockmoller J (2003) Variations in the 5-hydroxytryptamine type 3B receptor gene as predictors of the efficacy of antiemetic treatment in cancer patients. J Clin Oncol 21:2147–2155

    Article  PubMed  CAS  Google Scholar 

  • Warr DG, Hesketh PJ, Gralla RJ, Muss HB, Herrstedt J, Eisenberg PD, Raftopoulos H, Grunberg SM, Gabriel M, Rodgers A, Bohidar N, Klinger G, Hustad CM, Horgan KJ, Skobieranda F (2005) Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 23:2822–2830

    Article  PubMed  CAS  Google Scholar 

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The authors declare no conflict of interest.

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Correspondence to P. A. Fasching.

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P. A. Fasching and B. Kollmannsberger contributed equally to this work.

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Fasching, P.A., Kollmannsberger, B., Strissel, P.L. et al. Polymorphisms in the novel serotonin receptor subunit gene HTR3C show different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy. J Cancer Res Clin Oncol 134, 1079–1086 (2008).

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