Estrogen receptor genotypes, menopausal status, and the lipid effects of tamoxifen.
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.
Ntukidem
N I
NI
Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
Nguyen
A T
AT
Stearns
V
V
Rehman
M
M
Schott
A
A
Skaar
T
T
Jin
Y
Y
Blanche
P
P
Li
L
L
Lemler
S
S
Hayden
J
J
Krauss
R M
RM
Desta
Z
Z
Flockhart
D A
DA
Hayes
D F
DF
D000328:Adult; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D015331:Cohort Studies; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000097:blood / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000097:blood / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008055:Lipids / Q000097:blood*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D011446:Prospective Studies; D013629:Tamoxifen / Q000494:pharmacology*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008055:Lipids; D013629:Tamoxifen; D002784:Cholesterol; D019389:Cytochrome P-450 CYP2D6
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