[1]李璐,王明霞,赵宝华.细胞色素P450 2D6、3A4和19A1基因多态性与乳腺癌的药物治疗[J].中国药理学通报,2013,(03):311-314.
 LI Lu,WANG Ming xia,ZHAO Bao hua.Cytochrome P450 2D6, 3A4 and 19A1:gene polymorphism and drug therapy of breast cancer[J].Chinese Pharmacological Bulletin,2013,(03):311-314.
点击复制

细胞色素P450 2D6、3A4和19A1基因多态性与乳腺癌的药物治疗()
分享到:

《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2013年03期
页码:
311-314
栏目:
讲座与综述
出版日期:
2013-03-25

文章信息/Info

Title:
Cytochrome P450 2D6, 3A4 and 19A1:gene polymorphism and drug therapy of breast cancer
作者:
李璐12王明霞1赵宝华2
1. 河北医科大学第四医院; 2. 河北师范大学生命科学学院,河北 石家庄050011
Author(s):
LI Lu12 WANG Mingxia1 ZHAO Baohua2
1. the Fourth Hospital of Hebei Medical University; 2. College of Life Science, Hebei Normal University,Shijiazhuang050011,China
关键词:
细胞色素P450基因多态性药物治疗乳腺癌他莫昔芬芳香化酶抑制剂紫杉醇多西紫杉醇
Keywords:
cytochrome P450 gene polymorphism drug therapy breast cancer tamoxifen aromatase inhibitors paclitaxel docetaxel
分类号:
R05;R345.99;R394.2;R737.905
文献标志码:
A
摘要:
细胞色素P450(CYP)是一种重要的氧化代谢酶,参与多种药物的代谢。CYP酶具有基因多态性,对药物的代谢呈现明显的差异,对乳腺癌用药也有差异性影响。该文主要阐述细胞色素P450 2D6、3A4和19A1亚型的多态性,并就其多态性对临床乳腺癌治疗中重要的药物如他莫昔芬、芳香化酶抑制剂、紫杉醇类在治疗学方面的影响进行综述。
Abstract:
The cytochrome P450 (CYP), as an important enzyme of oxidative metabolism, is involed in metabolism of a variety of drugs. The polymorphic nature of CYP genes show obvious differences in metabolism of drugs, and also have an effect on drug responses of breast cancer therapy. This article focuses on the polymorphisms of cytochrome P450 2D6, 3A4 and 19A1 subtype,and reviews the effects of their polymorphisms on the major drugs in clinical breast cancer drug therapy, including tamoxifen, aromatase inhibitors, docetaxel and paclitaxel.

参考文献/References:

[1]Rendic S. Summary of information on human CYP enzymes: human P450 metabolism data [J]. Drug Metab Rev, 2002, 34(1-2): 83-484.
[2]IngelmanSundberg M, Sim S C, Gomez A, RodriguezAntona C. Influence of cytochrome P450 polymorphisms on drug therapies: pharmacogenetic, pharmacoepigenetic and clinical aspects [J]. Pharmacol Ther, 2007, 116(3):496-526.
[3]Zhou S F, Di Y M, Chan E, et al. Clinical pharmacogenetics and potential application in personalized medicine [J]. Curr Drug Metab, 2008,9(8):738-84.
[4]Zhou S F, Liu J P, Chowbay B. Polymorphism of human cytochrome P450 enzymes and its clinical impact [J]. Drug Metab Rev, 2009, 41(2): 89-295.
[5]IngelmanSundberg M. Genetic polymorphisms of cytochrome P450 2D6 (CYP2D6): clinical consequences,evolutionary aspects and functional diversity [J]. Pharmacogenomics J, 2005, 5(1):6-13.
[6]Goetz M P, Knox S K, Suman V J, et al. The impact of cytochrome P450 2D6 metabolism in women receiving adjuvant tamoxifen [J]. Breast Cancer Res Treat, 2007,101(1):113-21.
[7]Madlensky L, Natarajan L, Tchu S, et al. Tamoxifen metabolite concentrations, CYP2D6 genotype, and breast cancer outcomes [J]. Clin Pharmacol Ther, 2011, 89(5):718-25.
[8]Hayes D F, Stearns V, Rae J, et al. A model citizen is tamoxifen more effective than aromatase inhibitors if we pick the right patients? [J]. J Natl Cancer Inst, 2008,100(9):610-3.
[9]Schroth W, Antoniadou L, Fritz P, et al. Breast cancer treatment outcome with adjuvant tamoxifen relative to patient CYP2D6 and CYP2C19 genotypes [J]. J Clin Oncol, 2007, 25(33):5187-93.
[10]Azoulay L, Dell’Aniello S, Huiart L, et al. Concurrent use of tamoxifen with CYP2D6 inhibitors and the risk of breast cancer recurrence [J]. Breast Cancer Res Treat, 2011,126(3):695-703.
[11]Singh M S, Francis P A, Michael M. Tamoxifen, cytochrome P450 genes and breast cancer clinical outcomes [J]. Breast, 2011, 20(2):111-8.
[12]成碟, 徐为人, 刘昌孝. 细胞色素P450(CYP450)遗传多态性研究进展[J]. 中国药理学通报, 2006, 22(12): 1409-14.
[12]Cheng D, Xu W R, Liu C X. Progress of research on genetic polymorphism of CYP450s [J]. Chin Pharmacol Bull, 2006, 22(12): 1409-14.
[13]范江, 陆劲松. CYP19基因多态性与乳腺癌风险[J]. 国际肿瘤学杂志, 2006,33(2):128-31.
[13]Fan J, Lu J S. CYP19 gene polymorphism and the risk of breast cancer [J]. Int J Oncol, 2006, 33(2):128-31.
[14]王晓稼, 邵喜英. 乳腺癌CYP19基因研究进展[J]. 实用肿瘤杂志, 2007,22(2):178-81.
[14]Wang X J, Shao X Y. Progress in breast cancer CYP19 gene [J]. J Pract Oncol, 2007,22(2):178-81.
[15]Colomer R, Monzo M, Tusquets I, et al. A singlenucleotide polymorphism in the aromatase gene is associated with the efficacy of the aromatase inhibitor letrozole in advanced breast carcinoma [J]. Clin Cancer Res, 2008,14(3): 811-6.
[16]Ma C X, Adjei A A, Salavaggione O E, et al. Human aromatase: gene resequencing and functional genomics [J].Cancer Res, 2005, 65(23): 11071-82.
[17]Wang L, Ellsworth K A, Moon I, et al. Functional genetic polymorphisms in the aromatase gene CYP19 vary the response of breast cancer patients to neoadjuvant therapy with aromatase inhibitors [J]. Cancer Res, 2010, 70(1): 319-28.
[18]Fasching P A, Loehberg C R, Strissel P L, et al. Single nucleotide polymorphisms of the aromatase gene (CYP19A1), HER2/neu status, and prognosis in breast cancer patients [J]. Breast Cancer Res Treat, 2008, 112(1):89-98.
[19]Park I H, Lee Y S, Lee K S, et al. Single nucleotide polymorphisms of CYP19A1 predict clinical outcomes and adverse events associated with letrozole in patients with metastatic breast cancer [J]. Cancer Chemother Pharmacol, 2011,68(5): 1263-71.
[20]Zhou D, Afzelius L, Grimm S W, et al. Comparison of methods for the prediction of the metabolic sites for CYP3A4mediated metabolic reactions [J]. Drug Metab Dispos, 2006, 34(6): 976-83.
[21]Tran A, Jullien V, Alexandre J, et al. Pharmacokinetics and toxicity of docetaxel:Role of CYP3A, MDR1, and GST Polymorphisms [J].Clin Pharmacol Ther, 2006,79(6):570-80.
[22]Baker S D, Verweij J, Cusatis G A, et al. Pharmacogenetic pathway analysis of docetaxel elimination [J], Clin Pharmacol Ther, 2009, 85(2):155-63.
[23]Puisset F, Chatelut E, Dalenc F, et al. Dexamethasone as a probe for docetaxel clearance [J]. Cancer Chemother Pharmacol, 2004, 54(3): 265-72.
[24]Dandamudi U B, Adams L M, Johnson B, et al. Lack of effect of casopitant on the pharmacokinetics of docetaxel in patients with cancer [J]. Cancer Chemother Pharmacol, 2011, 67(4):783-90.
[25]van Schaik R H. CYP450 pharmacogenetics for personalizing cancer therapy [J]. Drug Resist Updat, 2008, 11(3):77-98.
[26]Nakajima Y, Yoshitani T, FukushimaUesaka H, et al. Impact of the haplotype CYP3A4*16B harboring the Thr185Ser substitution on paclitaxel metabolism in Japanese patients with cancer [J]. Clin Pharmacol Ther, 2006,80(2): 179-91.
[27]Zhou S F, Zhou Z W, Huang M. Polymorphisms of human cytochrome P450 2C9 and the functional relevance [J].Toxicology, 2010, 278(2):165-88.
[28]Pulczynska A, Lukaszkiewicz J, Wojnar M, et al. Cytochrome P450 polymorphismmolecular,metabolic and pharmacogenetic aspects. IV. Application of long polymerase chain reaction for identification of CYP2D6 gene duplication [J]. Acta Pol Pharm, 2011, 68(1):9-13.
[29]Barginear M F, Jaremko M, Peter I, et al. Increasing tamoxifen dose in breast cancer patients based on CYP2D6 genotypes and endoxifen levels: Effect on active metabolite isomers and the antiestrogenic activity score [J]. Clin Pharmacol Ther, 2011, 90(4):605-11.

相似文献/References:

[1]杨秀芬,钟正贤,廖梅春,等.蛇葡萄素与苯并芘合用对大鼠肺组织内CYP和GST基因表达的影响[J].中国药理学通报,2010,(01):135.
 YANG Xiu fen,ZHONG Zheng xian,LIAO Mei chun,et al.Effect of ampelopsis and benzo(a)pyrene coadministration on genes expression of CYP and GST in lung tissues of rats[J].Chinese Pharmacological Bulletin,2010,(03):135.
[2]马晶晶,李金恒,曹晓梅,等.基因多态性对奥美拉唑药动学与相对生物利用度的影响[J].中国药理学通报,2010,(02):258.
 MA Jing jing,LI Jin heng,CAO Xiao mei,et al.Effects of CYP2C19 polymorphism on pharmacokinetic profile and comparative bioavailability of omeprazole[J].Chinese Pharmacological Bulletin,2010,(03):258.
[3]杨静,乔海灵.过敏反应与HLA基因多态性[J].中国药理学通报,2008,(04):0.
 YANG Jing,QIAO Hai Ling.Correlation between allergy and HLA genetic polymorphism[J].Chinese Pharmacological Bulletin,2008,(03):0.
[4]杨静,乔海灵.青霉素特异性IgE抗体的种类与HLADRB基因多态性[J].中国药理学通报,2008,(06):0.
 YANG Jing,QIAO Hai ling.Correlation of HLADRB genetic locus with penicillinspecific IgE antibodies[J].Chinese Pharmacological Bulletin,2008,(03):0.
[5]陈豪,谭志荣,周宏灏.含黄素单氧化酶3(FMO3)结构、功能及其基因多态性的研究进展[J].中国药理学通报,2008,(10):0.
 CHEN Hao,TAN Zhi rong,ZHOU Hong hao.Advance in flavincontaining monooxygenase 3 (FMO3):structure/function and genetic polymorphisms[J].Chinese Pharmacological Bulletin,2008,(03):0.
[6]余敏,周宏灏,刘昭前.糖尿病肾病相关基因研究进展[J].中国药理学通报,2008,(11):0.
 YU Min,ZHOU Hong hao,LIU Zhao qian.Progress in related genes of diabetic nephropathy[J].Chinese Pharmacological Bulletin,2008,(03):0.
[7]李慧华,杨敏,余敏,等.β3AR Trp64Arg遗传多态性对T2DM患者罗格列酮疗效的影响[J].中国药理学通报,2009,(03):0.
 LI Hui hua,YANG Min,YU Min,et al.The effect of β3AR Trp64Arg on rosiglitazone response in T2DM patients[J].Chinese Pharmacological Bulletin,2009,(03):0.
[8]杨秀芬,钟正贤,廖梅春,等.蛇葡萄素与苯并芘合用对大鼠肝组织内CYP和GST基因表达的影响[J].中国药理学通报,2009,(07):0.
 YANG Xiu fen,ZHONG Zheng xian,LIAO Mei chun.Effect of ampelopsis and benzo(a)pyrene coadministration on gene expression of CYP and GST in liver tissues of rats[J].Chinese Pharmacological Bulletin,2009,(03):0.
[9]庄笑梅,林庆辉,李春正,等.罗通定在人、比格犬和大鼠肝微粒体代谢转化的体外比较研究[J].中国药理学通报,2009,(09):0.
 ZHUANG Xiao mei,LIN Qing hui,LI Chun zheng,et al.In vitro comparison of rotundine metabolism in liver microsomes of human,dog and rat[J].Chinese Pharmacological Bulletin,2009,(03):0.
[10]艾常虹,孙汉雄,李 桦,等.中药有效成分对细胞色素P450酶的抑制活性评价[J].中国药理学通报,2011,(04):519.
 AIChang-hong,SUN Han-xiong,LIHua,et al.In vitro inhibition of cytochrom e P450activities by active constituents of Chinese herbal drugs [J].Chinese Pharmacological Bulletin,2011,(03):519.

备注/Memo

备注/Memo:
收稿日期:2012-11-22,修回日期:2012-12-29 基金项目:河北省卫生厅医学科学研究重点课题项目(No 20100122);河北省人力资源和社会保障厅留学回国人员科技活动择优资助项目(No 20100313) 作者简介:李璐(1987-),女,硕士生,研究方向:药物相互作用,Email:liludoudou@yahoo.com.cn; 王明霞(1967-),女,主任药师,硕士生导师,研究方向:临床药学、临床药理学,通讯作者,Tel:031186095730,Email:mxia_wang@yahoo.com.cn
更新日期/Last Update: 2013-03-25