Estrogen receptor genotypes, menopausal status, and the lipid effects of tamoxifen

N. I. Ntukidem, A. T. Nguyen, V. Stearns, M. Rehman, A. Schott, T. Skaar, Y. Jin, P. Blanche, L. Li, S. Lemler, J. Hayden, R. M. Krauss, Z. Desta, D. A. Flockhart, D. F. Hayes

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Tamoxifen induces important changes in serum lipid profiles in some women; however, little information is available to predict which women will experience improved lipid profiles during tamoxifen therapy. As part of a multicenter prospective observational trial in 176 breast cancer patients, we tested the hypothesis that tamoxifen-induced lipid changes were associated with genetic variants in candidate target genes (CYP2D6, ESR1, and ESR2). Tamoxifen lowered low-density lipoprotein cholesterol (P<0.0001) by 23.5 mg/dl (13.5-33.5 mg/dl) and increased triglycerides (P=0.006). In postmenopausal women, the ESR1-XbaI and ESR2-02 genotypes were associated with tamoxifen-induced changes in total cholesterol (P=0.03; GG vs GA/AA) and triglycerides (P=0.01; gene-dose effect), respectively. In premenopausal women, the ESR1-XbaI genotypes were associated with tamoxifen-induced changes in triglycerides (P=0.002; gene-dose effect) and high-density lipoprotein (P=0.004; gene-dose effect). Our results suggest that estrogen receptor genotyping may be useful in predicting which women would benefit more from tamoxifen.

Original languageEnglish (US)
Pages (from-to)702-710
Number of pages9
JournalClinical Pharmacology and Therapeutics
Volume83
Issue number5
DOIs
StatePublished - May 30 2008

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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    Ntukidem, N. I., Nguyen, A. T., Stearns, V., Rehman, M., Schott, A., Skaar, T., Jin, Y., Blanche, P., Li, L., Lemler, S., Hayden, J., Krauss, R. M., Desta, Z., Flockhart, D. A., & Hayes, D. F. (2008). Estrogen receptor genotypes, menopausal status, and the lipid effects of tamoxifen. Clinical Pharmacology and Therapeutics, 83(5), 702-710. https://doi.org/10.1038/sj.clpt.6100343