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

doi:10.1038/sj.clpt.6100343

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

34 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 language	English (US)
Pages (from-to)	702-710
Number of pages	9
Journal	Clinical pharmacology and therapeutics
Volume	83
Issue number	5
DOIs	https://doi.org/10.1038/sj.clpt.6100343
State	Published - May 30 2008

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)

Access to Document

10.1038/sj.clpt.6100343

Cite this

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

@article{74be78172e75481fbd3eca8b226a08a1,

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

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.",

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

year = "2008",

month = may,

day = "30",

doi = "10.1038/sj.clpt.6100343",

language = "English (US)",

volume = "83",

pages = "702--710",

journal = "Clinical pharmacology and therapeutics",

issn = "0009-9236",

publisher = "Nature Publishing Group",

number = "5",

}

TY - JOUR

T1 - Estrogen receptor genotypes, menopausal status, and the lipid effects of tamoxifen

AU - Ntukidem, N. I.

AU - Nguyen, A. T.

AU - Stearns, V.

AU - Rehman, M.

AU - Schott, A.

AU - Skaar, T.

AU - Jin, Y.

AU - Blanche, P.

AU - Li, L.

AU - Lemler, S.

AU - Hayden, J.

AU - Krauss, R. M.

AU - Desta, Z.

AU - Flockhart, D. A.

AU - Hayes, D. F.

PY - 2008/5/30

Y1 - 2008/5/30

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=42349088390&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42349088390&partnerID=8YFLogxK

U2 - 10.1038/sj.clpt.6100343

DO - 10.1038/sj.clpt.6100343

M3 - Article

C2 - 17713466

AN - SCOPUS:42349088390

SN - 0009-9236

VL - 83

SP - 702

EP - 710

JO - Clinical pharmacology and therapeutics

JF - Clinical pharmacology and therapeutics

IS - 5

ER -

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

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this