This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tremblay, P.-B. Articles by Brockmöller, J. Search for Related Content PubMed PubMed Citation Articles by Tremblay, P.-B. Articles by Brockmöller, J. Social Bookmarking                            What's this?

Variations in the 5-Hydroxytryptamine Type 3B Receptor Gene as Predictors of the Efficacy of Antiemetic Treatment in Cancer Patients

Pierre-Benoit Tremblay, Rolf Kaiser, Orhan Sezer, Nadja Rösler, Claudia Schelenz, Kurt Possinger, Ivar Roots, Jürgen Brockmöller

From the Institute of Clinical Pharmacology and Department of Hematology and Oncology, University Medical Center Charité, Humboldt University of Berlin, Berlin; and Department of Clinical Pharmacology, University Medical Center of the Georg-August-University Göttingen, Göttingen, Germany.

Address reprint requests to Rolf Kaiser, MD, Abteilung für Klinische Pharmakologie, Universitätsklinikum der Georg-August Universität Göttingen, Robert Koch Str 40, D-37075 Göttingen; email: rolf.kaiser{at}med.uni-goettingen.de.

Purpose: Serotonin (5-hydroxytryptamine type 3 [5-HT₃]) receptor antagonists have substantially reduced but not eliminated nausea and vomiting in patients undergoing cancer chemotherapy. They act through specific binding to the 5-HT_3A, 5-HT_3B receptor complex. The 5-HT_3B subunit seems to be most important for its functionality. We hypothesized that patients with genetic variations in the 5-HT_3B receptor gene might respond differently to antiemetic treatment.

Patients and Methods: We included 242 cancer patients on their first day of chemotherapy. Nausea and vomiting were documented before and twice during the chemotherapy using standardized interviews and visual analog scales. We sequenced the entire 5-HT_3B receptor gene, including the 5` flanking region and at least a 20–base pair intronic sequence of each intron-exon splice site of all patients.

Results: Approximately 30% of all patients suffered from nausea or vomiting. Sequencing of the 5-HT_3B receptor gene revealed 13 polymorphisms: two of them were amino acid exchanges (Tyr129Ser, Ala223Thr) and two were deletion variants. In both observation periods, patients homozygous for the -100_-102delAAG deletion variant of the promotor region experienced vomiting more frequently than did all the other patients.

Conclusion: A more efficient antiemetic treatment with 5-HT₃ receptor antagonists might be possible on a pharmacogenetic basis. However, only a small fraction of the therapeutic failure is explained by the -AAG deletion variant of the 5-HT_3B receptor gene. Additional clinical and biochemical studies are needed to confirm the association.

Supported by the German Ministry for Education and Research, grant nos. 01EC9408 and 01ZZ9511, and the German Ministry for Research and Technology, Bonn, Germany, grant no. 01GG9845/5.

Pierre-Benoit Tremblay and Rolf Kaiser contributed equally to this work.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				F Skorpen, E. Laugsand, P Klepstad, and S Kaasa Variable response to opioid treatment: any genetic predictors within sight? Palliative Medicine, June 1, 2008; 22(4): 310 - 327. [Abstract] [PDF]

				K. Krzywkowski, P. A. Davies, P. L. Feinberg-Zadek, H. Brauner-Osborne, and A. A. Jensen High-frequency HTR3B variant associated with major depression dramatically augments the signaling of the human 5-HT3AB receptor PNAS, January 15, 2008; 105(2): 722 - 727. [Abstract] [Full Text] [PDF]

				R. R Shah Pharmacogenetics in drug regulation: promise, potential and pitfalls Phil Trans R Soc B, August 29, 2005; 360(1460): 1617 - 1638. [Abstract] [Full Text] [PDF]