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.
authors: Department of Medicine, Indiana University, Indianapolis, Indiana, USA.
authors: N I
authors: NI
authors: Ntukidem
authors: A T
authors: AT
authors: Nguyen
authors: V
authors: V
authors: Stearns
authors: M
authors: M
authors: Rehman
authors: A
authors: A
authors: Schott
authors: T
authors: T
authors: Skaar
authors: Y
authors: Y
authors: Jin
authors: P
authors: P
authors: Blanche
authors: L
authors: L
authors: Li
authors: S
authors: S
authors: Lemler
authors: J
authors: J
authors: Hayden
authors: R M
authors: RM
authors: Krauss
authors: Z
authors: Z
authors: Desta
authors: D A
authors: DA
authors: Flockhart
authors: D F
authors: DF
authors: Hayes
mesh_terms: 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*
chemical_list: D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D008055:Lipids; D013629:Tamoxifen; D002784:Cholesterol; D019389:Cytochrome P-450 CYP2D6
references: Clin Chem. 2000 Aug;46(8 Pt 1):1072-7
references: 10926885
references: Indian J Med Sci. 2001 Jul;55(7):359-65
references: 11883334
references: N Engl J Med. 2002 Mar 28;346(13):967-74
references: 11919305
references: Science. 2002 Mar 29;295(5564):2380-1
references: 11923515
references: Toxicol Lett. 2002 Feb 28;127(1-3):217-24
references: 12052661
references: JAMA. 2002 Jul 3;288(1):49-57
references: 12090862
references: Ann Intern Med. 2002 Jul 2;137(1):59-69
references: 12093250
references: N Engl J Med. 2004 Mar 11;350(11):1081-92
references: 15014181
references: N Engl J Med. 2004 Apr 8;350(15):1495-504
references: 15007110
references: JAMA. 2004 Apr 14;291(14):1701-12
references: 15082697
references: Breast Cancer Res Treat. 2004 May;85(2):151-9
references: 15111773
references: Circulation. 2004 Jun 15;109(23 Suppl 1):III2-7
references: 15198959
references: Clin Chem. 1972 Jun;18(6):499-502
references: 4337382
references: Pharmacol Ther. 1984;25(2):127-205
references: 6438654
references: Nature. 1986 Mar 13-19;320(6058):134-9
references: 3754034
references: Clin Chem. 1990 Jan;36(1):15-9
references: 2297909
references: Cancer. 1994 Feb 1;73(3):659-63
references: 8299087
references: Neoplasma. 1994;41(1):13-6
references: 8202188
references: J Natl Cancer Inst. 1994 Oct 19;86(20):1534-9
references: 7932809
references: Tumori. 1998 Nov-Dec;84(6):687-90
references: 10080678
references: J Clin Oncol. 1995 Dec;13(12):2900-5
references: 8523053
references: Cancer Biochem Biophys. 1995 Nov;15(2):83-90
references: 8590439
references: Proc Natl Acad Sci U S A. 1996 Jun 11;93(12):5925-30
references: 8650195
references: Atherosclerosis. 1996 Apr 5;121(2):217-29
references: 9125296
references: Endocrinology. 1997 Mar;138(3):863-70
references: 9048584
references: J Natl Cancer Inst. 1997 Jun 4;89(11):776-82
references: 9182975
references: N Engl J Med. 1998 Nov 26;339(22):1609-18
references: 9828250
references: Metabolism. 1998 Dec;47(12):1504-13
references: 9867082
references: Clin Pharmacol Ther. 1999 Jan;65(1):10-20
references: 9951426
references: J Natl Cancer Inst. 2005 Jan 5;97(1):30-9
references: 15632378
references: Lancet. 2005 Jan 1-7;365(9453):60-2
references: 15639680
references: Pharmacogenomics J. 2005;5(1):30-4
references: 15381922
references: J Clin Oncol. 2005 Jan 20;23(3):619-29
references: 15545664
references: Cancer. 2005 Mar 15;103(6):1114-21
references: 15712362
references: Cancer Chemother Pharmacol. 2005 May;55(5):471-8
references: 15685451
references: Gynecol Endocrinol. 2005 Jan;20(1):36-44
references: 15969245
references: Br J Cancer. 2005 Aug;93 Suppl 1:S23-7
references: 16100522
references: J Natl Cancer Inst. 2005 Sep 7;97(17):1262-71
references: 16145047
references: J Natl Cancer Inst. 2005 Nov 16;97(22):1652-62
references: 16288118
references: J Clin Oncol. 2005 Dec 20;23(36):9312-8
references: 16361630
references: N Engl J Med. 2005 Dec 29;353(26):2747-57
references: 16382061
references: Maturitas. 2006 May 20;54(2):119-26
references: 16242874
references: N Engl J Med. 2006 Jul 13;355(2):125-37
references: 16837676
references: Acta Paediatr. 2000 Jan;89(1):42-5
references: 10677056
references: Endocrinology. 1999 Dec;140(12):5566-78
references: 10579320
references: J Clin Endocrinol Metab. 1995 Nov;80(11):3191-5
references: 7593425