Estrogen receptor genotypes, menopausal status, and the effects of tamoxifen on lipid levels: revised and updated results.

D F Hayes, T C Skaar, J M Rae, N L Henry, A T Nguyen, V Stearns, L Li, S Philips, Z Desta, D A Flockhart, Consortium on Breast Cancer Pharmacogenomics (COBRA)

Clinical pharmacology and therapeutics 2010 Nov

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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.

Citation

D F Hayes, T C Skaar, J M Rae, N L Henry, A T Nguyen, V Stearns, L Li, S Philips, Z Desta, D A Flockhart, Consortium on Breast Cancer Pharmacogenomics (COBRA). Estrogen receptor genotypes, menopausal status, and the effects of tamoxifen on lipid levels: revised and updated results. Clinical pharmacology and therapeutics. 2010 Nov;88(5):626-9