Association of multiple drug resistance-1 gene polymorphism with multiple drug resistance in breast cancer patients from an ethnic Saudi Arabian population

被引:11
作者
Alsaif, Abdulaziz A. [1 ]
Hasan, Tarique N. [2 ]
Shafi, Gowhar [2 ]
Syed, Naveed A. [2 ]
Alsaif, Mohammed A. [3 ]
Al-Assaf, Abdullah H. [2 ]
Alshatwi, Ali A. [2 ]
机构
[1] King Saud Univ, Dept Surg, Coll Med, Riyadh 11451, Saudi Arabia
[2] King Saud Univ, Dept Food Sci & Nutr, Coll Food & Agr Sci, Mol Canc Biol Res Lab, Riyadh 11451, Saudi Arabia
[3] King Saud Univ, Dept Community Hlth Sci, Coll Appl Med Sci, Riyadh 11451, Saudi Arabia
关键词
Breast cancer; Biomarker; Drug resistance; MDR1; gene; SNP; Chemotherapy; Cyclophosphamide; Adriamycin; 5-Fluorouracil; Docetaxel; MDR1; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; CHEMOTHERAPY; EXPRESSION; YB-1;
D O I
10.1016/j.canep.2013.04.011
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Chemotherapy has been used widely to treat cancer, both as a systemic therapy and as a local treatment. Unfortunately, many types of cancer are still refractory to chemotherapy. The mechanisms of anticancer drug resistance have been extensively explored but have not been fully characterized. This study analyzed the occurrences of polymorphism (SNP) in the MDR1 gene in breast cancer patients and determined a possible association with chemotherapy. The study group included one hundred breast carcinoma patients who subsequently received chemotherapy (the regimen generally consisted of commonly used drugs such as cyclophosphamide, adriamycin, 5-fluorouracil, docetaxel and their combinations). Blood samples from 100 healthy individuals are used, as controls were also genotyped for the MDR1 gene. This investigation revealed a significant correlation with response to various regimens of chemotherapy showing a low response to therapy with the CT/TT genotype at (exon 12) 1236 codon (p < 0.001). These findings demonstrate, for the first time, that the polymorphisms in (exon 12) 1236 codon of the MDR1 gene greatly influence the drug response in patients from the Arab population of Saudi Arabia. (C) 2013 Elsevier Ltd. All rights reserved.
引用
收藏
页码:762 / 766
页数:5
相关论文
共 28 条
[1]  
Alshatwi AA, 2011, BREAST J, V18
[3]   Biochemical, cellular, and pharmacological aspects of the multidrug transporter [J].
Ambudkar, SV ;
Dey, S ;
Hrycyna, CA ;
Ramachandra, M ;
Pastan, I ;
Gottesman, MM .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 1999, 39 :361-398
[4]   Nuclear localization and increased levels of transcription factor YB-1 in primary human breast cancers are associated with intrinsic MDR1 gene expression [J].
Bargou, RC ;
Jurchott, K ;
Wagener, C ;
Bergmann, S ;
Metzner, S ;
Bommert, K ;
Mapara, MY ;
Winzer, KJ ;
Dietel, M ;
Dorken, B ;
Royer, HD .
NATURE MEDICINE, 1997, 3 (04) :447-450
[5]  
Bruce TJ, 1997, JNCI-J NATL CANCER I, V89, P917
[6]   Systemic treatment and liver transplantation for hepatocellular carcinoma: two ends of the therapeutic spectrum [J].
Burroughs, A ;
Hochhauser, D ;
Meyer, T .
LANCET ONCOLOGY, 2004, 5 (07) :409-418
[7]   Cancer drug resistance: The central role of the karyotype [J].
Duesberg, Peter ;
Li, Ruhong ;
Sachs, Rainer ;
Fabarius, Alice ;
Upender, Madhvi B. ;
Hehlmann, Ruediger .
DRUG RESISTANCE UPDATES, 2007, 10 (1-2) :51-58
[8]   Multiple paths to a drug resistance phenotype: Mutations, translocations, deletions and amplification of coding genes or promoter regions, epigenetic changes and microRNAs [J].
Fojo, Tito .
DRUG RESISTANCE UPDATES, 2007, 10 (1-2) :59-67
[9]   Epigenetics as a mechanism driving polygenic clinical drug resistance [J].
Glasspool, RM ;
Teodoridis, JM ;
Brown, R .
BRITISH JOURNAL OF CANCER, 2006, 94 (08) :1087-1092
[10]  
Hasan TN, 2012, CLIN TRANSL ONCOL