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- Title
PII-21.
- Authors
Hwang, J.; Jin, Y.; Storniolo, A. M.; Hayes, D. F.; Li, L.; Stearn, V.; Skaar, T. C.; Flockhart, D. A.
- Abstract
Background: Hot flashes are the most common side effect in women treated with tamoxifen, but their severity is variable. Since serotonin is thought to be involved in hot flashes, we determined the association of hot flashes with polymorphisms of four serotonin related genes in women taking tamoxifen.Methods: We studied 190 breast cancer patients before and after 1 & 4 months of tamoxifen therapy. At each time point, hot flash frequency and severity and current medication were recorded. The 5-HTTLPR variant in serotonin transporter, C(-1019)G polymorphism in serotonin 1A receptor (HTR1A), T102C in serotonin 2A receptor (HTR2A), and A218C in tryptophan hydroxylase1 (TPH1) were studied. Associations were analyzed by log-linear regression with repeated measures.Results: Before tamoxifen therapy, premenopausal subjects with previous chemotherapy with 5-HTTLPR ss genotype had higher hot flash scores than those with ll or Is genotype (P=0.04). In peri & postmenopausal subjects, hot flash scores of ss genotype increased more during tamoxifen therapy (P=0.02) and HTR2A TT genotype had higher hot flash scores before (P =0.02) and after (P=0.001) tamoxifen therapy than TC and CC. SSRIs appeared to be less effective at reducing hot flashes in HTR2A TT genotype patients (P=0.04). HTR1A and TPH1 were not associated with hot flashes.Conclusions: A pharmacogenetic interaction between tamoxifen and the serotonin transporter and HTR2A may contribute to the variability in tamoxifen induced hot flashes.Clinical Pharmacology & Therapeutics (2005) 79, P42–P42; doi: 10.1016/j.clpt.2005.12.146
- Subjects
PHARMACEUTICAL research; SEROTONIN; TAMOXIFEN; DRUG side effects; PHARMACOLOGY
- Publication
Clinical Pharmacology & Therapeutics, 2006, Vol 79, Issue 2, pP42
- ISSN
0009-9236
- Publication type
Article
- DOI
10.1016/j.clpt.2005.12.146