In:
Pharmacogenomics, Future Medicine Ltd, Vol. 11, No. 7 ( 2010-07), p. 943-950
Abstract:
Aims: Serotonin (5-hydroxytryptamine 3; 5-HT 3 ) receptors are involved in chemotherapy-induced nausea and vomiting (CINV), and 5-HT 3 antagonists are part of the ‘gold standard’ antiemetic treatment during chemotherapy. We investigated the correlation of common variants in 5-HT 3 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-HT 3 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-HT 3 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.
Type of Medium:
Online Resource
ISSN:
1462-2416
,
1744-8042
Language:
English
Publisher:
Future Medicine Ltd
Publication Date:
2010
SSG:
15,3
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