Tingyu Wang1, Yitian Zhou2, Guosheng Cao3. 1. College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. 2. Department of Physiology and Pharmacology, Karolinska Institutet, 17177, Stockholm, Sweden. 3. College of Pharmacy, Hubei University of Chinese Medicine, Wuhan, 430065, China. caoguosheng2006@163.com.
Abstract
BACKGROUND: Compared with western countries, Asian breast cancer patients have unique pathological and biological characteristics. Most of them are premenopausal women with HR positive. Tamoxifen as the first-line drug for premenopausal women with HR+ is involved in multiple enzymes and transporters during metabolizing and transporting process. Variants that cause decreased or inactive gene products leading to abnormal responses in tamoxifen therapy have well been studied in western countries, whereas such information is much less reported in Asian populations. OBJECTIVE: In order to elucidate the relationship between genetic variants and tamoxifen-induced individual drug reactions in different Asian populations and further identify genotypes/phenotypes with potential therapeutic significance. METHODS: We reviewed the frequencies of genetic variants in major enzymes and transporter genes involved in the metabolism and transport of tamoxifen across Asian populations as well as significant correlations between genotypes/metabolic phenotypes and metabolites concentrations or BC clinical outcomes. RESULTS: Significant inter-ethnic differences in allele frequencies was found among Asian populations, such as CYP2D6*4, *10, *41, CYP2C9*2, ABCB1 C3435T and SLCO1B1*5, and CYP2D6*10/*10 is the most common genotype correlated with adverse clinical outcomes. Moreover, we summarized the barriers and controversies of implementing pharmacogenetics in tamoxifen therapy and concluded that more population-specific pharmacogenetic studies are needed in the future. CONCLUSION: This review revealed more systematic pharmacogenomics of genes involved in the metabolism and transport besides CYP2D6, are required to optimize the genotyping strategies and guide the personalized tamoxifen therapy in Asian populations.
BACKGROUND: Compared with western countries, Asian breast cancer patients have unique pathological and biological characteristics. Most of them are premenopausal women with HR positive. Tamoxifen as the first-line drug for premenopausal women with HR+ is involved in multiple enzymes and transporters during metabolizing and transporting process. Variants that cause decreased or inactive gene products leading to abnormal responses in tamoxifen therapy have well been studied in western countries, whereas such information is much less reported in Asian populations. OBJECTIVE: In order to elucidate the relationship between genetic variants and tamoxifen-induced individual drug reactions in different Asian populations and further identify genotypes/phenotypes with potential therapeutic significance. METHODS: We reviewed the frequencies of genetic variants in major enzymes and transporter genes involved in the metabolism and transport of tamoxifen across Asian populations as well as significant correlations between genotypes/metabolic phenotypes and metabolites concentrations or BC clinical outcomes. RESULTS: Significant inter-ethnic differences in allele frequencies was found among Asian populations, such as CYP2D6*4, *10, *41, CYP2C9*2, ABCB1 C3435T and SLCO1B1*5, and CYP2D6*10/*10 is the most common genotype correlated with adverse clinical outcomes. Moreover, we summarized the barriers and controversies of implementing pharmacogenetics in tamoxifen therapy and concluded that more population-specific pharmacogenetic studies are needed in the future. CONCLUSION: This review revealed more systematic pharmacogenomics of genes involved in the metabolism and transport besides CYP2D6, are required to optimize the genotyping strategies and guide the personalized tamoxifen therapy in Asian populations.
Authors: Wendy Lorizio; Alan H B Wu; Mary S Beattie; Hope Rugo; Simone Tchu; Karla Kerlikowske; Elad Ziv Journal: Breast Cancer Res Treat Date: 2011-12-30 Impact factor: 4.872
Authors: Yan Jin; Zeruesenay Desta; Vered Stearns; Bryan Ward; Herbert Ho; Kyung-Hoon Lee; Todd Skaar; Anna Maria Storniolo; Lang Li; Adjei Araba; Rebecca Blanchard; Anne Nguyen; Lynda Ullmer; Jill Hayden; Suzanne Lemler; Richard M Weinshilboum; James M Rae; Daniel F Hayes; David A Flockhart Journal: J Natl Cancer Inst Date: 2005-01-05 Impact factor: 13.506
Authors: L Madlensky; L Natarajan; S Tchu; M Pu; J Mortimer; S W Flatt; D M Nikoloff; G Hillman; M R Fontecha; H J Lawrence; B A Parker; A H B Wu; J P Pierce Journal: Clin Pharmacol Ther Date: 2011-03-23 Impact factor: 6.875
Authors: Melinda L Telli; Ellen T Chang; Allison W Kurian; Theresa H M Keegan; Laura A McClure; Daphne Lichtensztajn; James M Ford; Scarlett L Gomez Journal: Breast Cancer Res Treat Date: 2010-10-19 Impact factor: 4.872
Authors: Vered Stearns; Michael D Johnson; James M Rae; Alan Morocho; Antonella Novielli; Pankaj Bhargava; Daniel F Hayes; Zeruesenay Desta; David A Flockhart Journal: J Natl Cancer Inst Date: 2003-12-03 Impact factor: 13.506
Authors: Anna Mueller-Schoell; Robin Michelet; Lena Klopp-Schulze; Madelé van Dyk; Thomas E Mürdter; Matthias Schwab; Markus Joerger; Wilhelm Huisinga; Gerd Mikus; Charlotte Kloft Journal: Cancers (Basel) Date: 2021-05-18 Impact factor: 6.639