ER-alpha and ER-beta genotypes predict tamoxifen effects on serum lipids in breast cancer patients

Abstract

Therapy with tamoxifen has been shown to be associated with favorable changes in lipid profile. We examined the relationship between genetic polymorphisms in estrogen receptor genes (ER-alpha and ER-beta) and serum lipid profile in 82 women who were prescribed tamoxifen (20mg/day). The fasting serum lipid profiles were evaluated before starting tamoxifen therapy and at the end of four months of treatment. Pvu II and Xba I RFLPs were used to identify the IVS1-401 and IVS1-354 polymorphisms of ER-alpha. Genotyping for the ER-beta single nucleotide polymorphism located in 3' UTR (dbSNP ID: rs4986938) was performed by a TaqMan assay. After four months of tamoxifen therapy all women had significantly lower LDL-cholesterol compared to baseline and the effect appeared more pronounced in postmenopausal women (p=0.03 and <0.0001 for pre- and postmenopausal women respectively). In the postmenopausal women, those with ER-alpha IVS1-401 C/C genotype had significantly lower total and LDL-cholesterol when compared to those with C/T and T/T genotypes (p= 0.014 and 0.017 for total cholesterol and LDL-cholesterol respectively). In the subgroup of postmenopausal women with ER-alpha IVS1-401 C/C genotype, those carrying ER-beta G/G genotype (dbSNP ID: rs4986938) had the most augmented response of LDL-cholesterol to tamoxifen therapy when compared to other groups (p=0.03). This pattern of genotypes may identify a group of women most likely to experience cardiovascular benefits from tamoxifen. Clinical Pharmacology & Therapeutics (2004) 75, P2–P2; doi: 10.1016/j.clpt.2003.11.005