Estrogen receptor genotypes, menopausal status, and the effects of tamoxifen on lipid levels: revised and updated results.
We previously reported that the ESR1 XbaI genotypes were associated with baseline and tamoxifen-induced serum lipid profiles. The analysis in that study was carried out by PCR followed by restriction-enzyme digestion. After reanalysis using more robust TaqMan assays, the findings related to ~10% of the genotypes for the ESR1 XbaI single-nucleotide polymorphism (SNP) were revised. For the other genotypes (i.e., ESR1 PvuII, ESR2, and CYP2D6), the results were nearly identical to those in the previous study. Upon reanalysis, previously reported associations between the ESR1 Xba1 genotypes and baseline triglyceride and low-density lipoprotein (LDL) cholesterol levels were no longer observed. Previously reported associations between the ESR1 XbaI genotypes and tamoxifen-induced changes in levels of total cholesterol, triglycerides, and high-density lipoprotein (HDL) cholesterol were also no longer observed. However, the following observations from the original report did not change: (i) the levels of circulating lipids are lower in women taking tamoxifen; (ii) there is an association between the ESR2-02 genotypes and changes in triglyceride levels; and (iii) neither ESR1 PvuII nor CYP2D6 is associated with any changes in serum lipid concentrations in patients receiving treatment with tamoxifen.
Hayes
D F
DF
Department of Internal Medicine and Breast Oncology Program, Comprehensive Cancer Center, University of Michigan Health and Hospitals System, Ann Arbor, Michigan, USA. hayesdf@umich.edu
Skaar
T C
TC
Rae
J M
JM
Henry
N L
NL
Nguyen
A T
AT
Stearns
V
V
Li
L
L
Philips
S
S
Desta
Z
Z
Flockhart
D A
DA
D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D047629:Estrogen Receptor beta / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D017697:Premenopause; D015203:Reproducibility of Results; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D013629:Tamoxifen / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014280:Triglycerides / Q000097:blood
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008055:Lipids; D020845:Selective Estrogen Receptor Modulators; D014280:Triglycerides; D013629:Tamoxifen; D002784:Cholesterol; D019389:Cytochrome P-450 CYP2D6
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