Impact of CYP2D6, CYP3A5, CYP2C9 and CYP2C19 polymorphisms on tamoxifen pharmacokinetics in Asian breast cancer patients

British Journal of Clinical Pharmacology

Volumn 71, Issue 5, 2011, Pages 737-750

  Lim, Joanne S L ^a,c   Chen, Xiang A ^a   Singh, Onkar ^a   Yap, Yoon S ^b   Ng, Raymond C H ^b   Wong, Nan S ^b   Wong, Mabel ^b   Lee, Edmund J D ^c   Chowbay, Balram ^a  

^a Humphrey Oei Institute of Cancer Research   (Singapore)

^b DIVISION OF MEDICAL ONCOLOGY   (Singapore)

^c NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

Author keywords

CYP2C19; CYP2D6; CYP3A5; Pharmacogenetics; Pharmacokinetics; Tamoxifen

Indexed keywords

CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A5; DRUG METABOLITE; GENOMIC DNA; TAMOXIFEN;

ARTICLE; ASIAN; BREAST CANCER; CANCER CHEMOTHERAPY; CANCER PATIENT; CHINESE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG METABOLISM; ETHNIC GROUP; GENETIC POLYMORPHISM; GENOTYPE; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; INDIA; MAJOR CLINICAL STUDY; MALAYSIA; PHARMACOGENETICS; PRIORITY JOURNAL;

ADULT; AGED; ANTINEOPLASTIC AGENTS, HORMONAL; ARYL HYDROCARBON HYDROXYLASES; ASIAN CONTINENTAL ANCESTRY GROUP; BREAST NEOPLASMS; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; CYTOCHROME P-450 ENZYME SYSTEM; FEMALE; HUMANS; MIDDLE AGED; POLYMORPHISM, GENETIC; PROSPECTIVE STUDIES; TAMOXIFEN;

EID: 79953848236     PISSN: 03065251     EISSN: 13652125     Source Type: Journal    
DOI: 10.1111/j.1365-2125.2011.03905.x     Document Type: Article

References (31)

1. Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 2005; 365: 1687-717.
2. Johnson MD, Zuo H, Lee KH, Trebley JP, Rae JM, Weatherman RV, Desta Z, Flockhart DA, Skaar TC. Pharmacological characterization of 4-hydroxy-N-desmethyl tamoxifen, a novel active metabolite of tamoxifen. Breast Cancer Res Treat 2004; 85: 151-9.
3. Stearns V, Johnson MD, Rae JM, Morocho A, Novielli A, Bhargava P, Hayes DF, Desta Z, Flockhart DA. Active tamoxifen metabolite plasma concentrations after coadministration of tamoxifen and the selective serotonin reuptake inhibitor paroxetine. J Natl Cancer Inst 2003; 95: 1758-64.
4. Crewe HK, Ellis SW, Lennard MS, Tucker GT. Variable contribution of cytochromes P450 2D6, 2C9 and 3A4 to the 4-hydroxylation of tamoxifen by human liver microsomes. Biochem Pharmacol 1997; 53: 171-8.
5. Schroth W, Antoniadou L, Fritz P, Schwab M, Muerdter T, Zanger UM, Simon W, Eichelbaum M, Brauch H. Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes. J Clin Oncol 2007; 25: 5187-93.
6. Goetz MP, Rae JM, Suman VJ, Safgren SL, Ames MM, Visscher DW, Reynolds C, Couch FJ, Lingle WL, Flockhart DA, Desta Z, Perez EA, Ingle JN. Pharmacogenetics of tamoxifen biotransformation is associated with clinical outcomes of efficacy and hot flushes. J Clin Oncol 2005; 23: 9312-8.
7. Schroth W, Goetz MP, Hamann U, Fasching PA, Schmidt M, Winter S, Fritz P, Simon W, Suman VJ, Ames MM, Safgren SL, Kuffel MJ, Ulmer HU, Boländer J, Strick R, Beckmann MW, Koelbl H, Weinshilboum RM, Ingle JN, Eichelbaum M, Schwab M, Brauch H. Association between CYP2D6 polymorphisms and outcomes among women with early stage breast cancer treated with tamoxifen. JAMA 2009; 302: 1429-36.
8. Burstein HJ, Prestrud AA, Seidenfeld J, Anderson H, Buchholz TA, Davidson NE, Gelmon KE, Giordano SH, Hudis CA, Malin J, Mamounas EP, Rowden D, Solky AJ, Sowers MR, Stearns V, Winer EP, Somerfield MR, Griggs JJ. American Society of Clinical Oncology Clinical Practice Guideline: Update on adjuvant endocrine therapy for women with hormone receptor-positive breast cancer. J Clin Oncol 2010; 28: 3784-96.
9. Jin Y, Desta Z, Stearns V, Ward B, Ho H, Lee KH, Skaar T, Storniolo AM, Li L, Araba A, Blanchard R, Nguyen A, Ullmer L, Hayden J, Lemler S, Weinshilboum RM, Rae JM, Hayes DF, Flockhart DA. CYP2D6 genotype, antidepressant use, and tamoxifen metabolism during adjuvant breast cancer treatment. J Natl Cancer Inst 2005; 97: 30-9.
10. Bradford LD. CYP2D6 allele frequency in European Caucasians, Asians, Africans and their descendants. Pharmacogenomics 2002; 3: 229-43.
11. Gough AC, Miles JS, Spurr NK, Moss JE, Gaedigk A, Eichelbaum M, Wolf CR. Identification of the primary gene defect at the cytochrome P450 CYP2D locus. Nature 1990; 347: 773-6.
12. Hanioka N, Kimura S, Meyer UA, Gonzalez FJ. The human CYP2D locus associated with a common genetic defect in drug oxidation: a G1934 - a base change in intron 3 of a mutant CYP2D6 allele results in an aberrant 3' splice recognition site. Am J Hum Genet 1990; 47: 994-1001.
13. Borges S, Desta Z, Li L, Skaar TC, Ward BA, Nguyen A, Jin Y, Storniolo AM, Nikoloff DM, Wu L, Hillman G, Hayes DF, Stearns V, Flockhart DA. Quantitative effect of CYP2D6 genotype and inhibitors on tamoxifen metabolism: implication for optimization of breast cancer treatment. Clin Pharmacol Ther 2006; 80: 61-74.
14. Gjerde J, Hauglid M, Breilid H, Lundgren S, Varhaug JE, Kisanga ER, Mellgren G, Steen VM, Lien EA. Effects of CYP2D6 and SULT1A1 genotypes including SULT1A1 gene copy number on tamoxifen metabolism. Ann Oncol 2008; 19: 56-61.
15. Sistonen J, Fuselli S, Palo JU, Chauhan N, Padh H, Sajantila A. Pharmacogenetic variation at CYP2C9, CYP2C19, and CYP2D6 at global and microgeographic scales. Pharmacogenet Genomics 2009; 19: 170-9.
16. Gaedigk A, Blum M, Gaedigk R, Eichelbaum M, Meyer UA. Deletion of the entire cytochrome P450 CYP2D6 gene as a cause of impaired drug metabolism in poor metabolizers of the debrisoquine/sparteine polymorphism. Am J Hum Genet 1991; 48: 943-50.
17. Myrand SP, Sekiguchi K, Man MZ, Lin X, Tzeng RY, Teng CH, Hee B, Garrett M, Kikkawa H, Lin CY, Eddy SM, Dostalik J, Mount J, Azuma J, Fujio Y, Jang IJ, Shin SG, Bleavins MR, Williams JA, Paulauskis JD, Wilner KD. Pharmacokinetics/genotype associations for major cytochrome P450 enzymes in native and first- and third-generation Japanese populations: comparison with Korean, Chinese, and Caucasian populations. Clin Pharmacol Ther 2008; 84: 347-61.
18. Wang SL, Huang JD, Lai MD, Liu BH, Lai ML. Molecular basis of genetic variation in debrisoquine hydroxylation in Chinese subjects: polymorphism in RFLP and DNA sequence of CYP2D6. Clin Pharmacol Ther 1993; 53: 410-8.
19. Lim HS, Ju Lee H, Seok Lee K, Sook Lee E, Jang IJ, Ro J. Clinical implications of CYP2D6 genotypes predictive of tamoxifen pharmacokinetics in metastatic breast cancer. J Clin Oncol 2007; 25: 3837-45.
20. Crewe HK, Notley LM, Wunsch RM, Lennard MS, Gillam EMJ. Metabolism of tamoxifen by recombinant human cytochrome P450 enzymes: formation of the 4-hydroxy, 4'-hydroxy and N-desmethyl metabolites and isomerization of trans-4-hydroxytamoxifen. Drug Metab Dispos 2002; 30: 869-74.
21. Kuehl P, Zhang J, Lin Y, Lamba J, Assem M, Schuetz J, Watkins PB, Daly A, Wrighton SA, Hall SD, Maurel P, Relling M, Brimer C, Yasuda K, Venkataramanan R, Strom S, Thummel K, Boguski MS, Schuetz E. Sequence diversity in CYP3A promoters and characterization of the genetic basis of polymorphic CYP3A5 expression. Nat Genet 2001; 27: 383-91.
22. Ingelman-Sundberg M, Oscarson M, McLellan RA. Polymorphic human cytochrome P450 enzymes: an opportunity for individualized drug treatment. Trends Pharmacol Sci 1999; 20: 342-9.
23. Balram C, Zhou Q, Cheung YB, Lee EJD. CYP3A5*3 and *6 single nucleotide polymorphisms in three distinct Asian populations. Eur J Clin Pharmacol 2003; 59: 123-6.
24. Roy JN, Lajoie J, Zijenah LS, Barama A, Poirier C, Ward BJ, Roger M. CYP3A5 genetic polymorphisms in different ethnic populations. Drug Metab Dispos 2005; 33: 884-7.
25. King BP, Leathart JBS, Mutch E, Williams FM, Daly AK. CYP3A5 phenotype-genotype correlations in a British population. Br J Clin Pharmacol 2003; 55: 625-9.
26. Lee KH, Ward BA, Desta Z, Flockhart DA, Jones DR. Quantification of tamoxifen and three metabolites in plasma by high-performance liquid chromatography with fluorescence detection: application to a clinical trial. J Chromatogr B Analyt Technol Biomed Life Sci 2003; 791: 245-53.
27. Zhu YB, Zhang Q, Zou JJ, Yu CX, Xiao DW. Optimizing high-performance liquid chromatography method with fluorescence detection for quantification of tamoxifen and two metabolites in human plasma: application to a clinical study. J Pharm Biomed Anal 2008; 46: 349-55.
28. Xu Y, Sun Y, Yao L, Shi L, Wu Y, Ouyang T, Li J, Wang T, Fan Z, Fan T, Lin B, He L, Li P, Xie Y. Association between CYP2D6 *10 genotype and survival of breast cancer patients receiving tamoxifen treatment. Ann Oncol 2008; 19: 1423-9.
29. Schroth W, Hamann U, Fasching PA, Dauser S, Winter S, Eichelbaum M, Schwab M, Brauch H. CYP2D6 polymorphisms as predictors of outcome in breast cancer patients treated with tamoxifen: expanded polymorphism coverage improves risk stratification. Clin Cancer Res 2010; 16: 4468-77.
30. Tucker AN, Tkaczuk KA, Lewis LM, Tomic D, Lim CK, Flaws JA. Polymorphisms in cytochrome P4503A5 (CYP3A5) may be associated with race and tumor characteristics, but not metabolism and side effects of tamoxifen in breast cancer patients. Cancer Lett 2005; 217: 61-72.
31. Li-Wan-Po A, Girard T, Farndon P, Cooley C, Lithgow J. Pharmacogenetics of CYP2C19: functional and clinical implications of a new variant CYP2C19*17. Br J Clin Pharmacol 2010; 69: 222-30.