Research Article

Polymorphism in HTR3D shows different risks for acute chemotherapy-induced vomiting after anthracycline chemotherapy

Christian Hammer

Institute of Human Genetics, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany

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Peter A Fasching

University Breast Center Franconia, Erlangen University Hospital, Universitaetsstr. 21–23, 91054 Erlangen, Germany

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Christian R Loehberg

University Breast Center Franconia, Erlangen University Hospital, Universitaetsstr. 21–23, 91054 Erlangen, Germany

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Claudia Rauh

University Breast Center Franconia, Erlangen University Hospital, Universitaetsstr. 21–23, 91054 Erlangen, Germany

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Arif B Ekici

University Breast Center Franconia, Erlangen University Hospital, Universitaetsstr. 21–23, 91054 Erlangen, Germany

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Sebastian M Jud

University Breast Center Franconia, Erlangen University Hospital, Universitaetsstr. 21–23, 91054 Erlangen, Germany

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Mayada R Bani

University Breast Center Franconia, Erlangen University Hospital, Universitaetsstr. 21–23, 91054 Erlangen, Germany

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Matthias W Beckmann

University Breast Center Franconia, Erlangen University Hospital, Universitaetsstr. 21–23, 91054 Erlangen, Germany

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Reiner Strick

University Breast Center Franconia, Erlangen University Hospital, Universitaetsstr. 21–23, 91054 Erlangen, Germany

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Beate Niesler

† Author for correspondence

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Email the corresponding author at beate.niesler@med.uni-heidelberg.de

Published Online:6 Jul 2010https://doi.org/10.2217/pgs.10.67

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Abstract

Aims: Serotonin (5-hydroxytryptamine 3; 5-HT₃) receptors are involved in chemotherapy-induced nausea and vomiting (CINV), and 5-HT₃ antagonists are part of the ‘gold standard’ antiemetic treatment during chemotherapy. We investigated the correlation of common variants in 5-HT₃ receptor subunit genes with the occurrence of CINV. Materials & methods: A total of 110 previously characterized chemotherapy-naive women with primary breast cancer treated with anthracycline-containing chemotherapy served as a study group for mutational analysis by direct sequencing. Eight common SNPs in the 5-HT₃ receptor genes, HTR3A, HTR3B, HTR3D and HTR3E, were selected for association analysis. Results: A nonsynonymous variant in HTR3D, p.G36A (rs6443930), was found to be over-represented in nonresponders, assuming a log-additive inheritance model (p = 0.048). Cox proportional regression analysis resulted in a hazards ratio of 0.36 for homozygous carriers of the C allele to vomit within 24 h after first chemotherapy administration (p = 0.049). Conclusion: Our data supports the hypothesis that 5-HT₃ receptors play an important role in the pathogenesis of CINV. Along with previously identified HTR3 polymorphisms, the HTR3D p.G36A variant could also contribute to facilitating individual risk predictions.

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Papers of special note have been highlighted as: ▪ of interest ▪▪ of considerable interest

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Vol. 11, No. 7

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History

Published online 6 July 2010

Published in print July 2010

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Acknowledgements

The authors would like to acknowledge the generosity of the patients for participating in this study. We thank Elke Fenner for excellent technical assistance, and Claire Bacon for helpful discussion.

Financial & competing interests disclosure

This work was supported by the German Cancer Aid (107229 to Beate Niesler). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

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