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

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...

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Hauptverfasser: Hammer, Christian (VerfasserIn) , Fasching, Peter Andreas (VerfasserIn) , Loehberg, Christian R (VerfasserIn) , Rauh, Claudia (VerfasserIn) , Ekici, Arif B. (VerfasserIn) , Jud, Sebastian M. (VerfasserIn) , Bani, Mayada R. (VerfasserIn) , Beckmann, Matthias Wilhelm (VerfasserIn) , Strick, Reiner (VerfasserIn) , Niesler, Beate (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 6 Jul 2010
In: Pharmacogenomics
Year: 2010, Jahrgang: 11, Heft: 7, Pages: 943-950
ISSN:1744-8042
DOI:10.2217/pgs.10.67
Online-Zugang:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.2217/pgs.10.67
Verlag, lizenzpflichtig, Volltext: https://www.futuremedicine.com/doi/10.2217/pgs.10.67
Volltext
Verfasserangaben:Christian Hammer, Peter A. Fasching, Christian R. Loehberg, Claudia Rauh, Arif B. Ekici, Sebastian M. Jud, Mayada R. Bani, Matthias W. Beckmann, Reiner Strick & Beate Niesler

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520 |a 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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