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多药耐药-1 基因多态性与沙特阿拉伯裔乳腺癌患者多药耐药的相关性。

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

机构信息

Department of Surgery, College of Medicine, King Saud University, Riyadh, Saudi Arabia.

出版信息

Cancer Epidemiol. 2013 Oct;37(5):762-6. doi: 10.1016/j.canep.2013.04.011. Epub 2013 May 29.

DOI:10.1016/j.canep.2013.04.011
PMID:23725642
Abstract

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.

摘要

化疗已被广泛用于治疗癌症,包括全身治疗和局部治疗。不幸的是,许多类型的癌症仍然对化疗有抗药性。抗癌药物耐药性的机制已经被广泛研究,但尚未完全阐明。本研究分析了乳腺癌患者 MDR1 基因的多态性(SNP)的发生情况,并确定了其与化疗的可能相关性。研究组包括 100 名随后接受化疗的乳腺癌患者(方案通常包括环磷酰胺、阿霉素、5-氟尿嘧啶、多西他赛等常用药物及其组合)。还对 100 名健康个体的血液样本进行了基因分型,作为对照。这项研究表明,与不同化疗方案的反应有显著相关性,在(外显子 12)1236 密码子处 CT/TT 基因型对治疗的反应较低(p<0.001)。这些发现首次表明,MDR1 基因(外显子 12)1236 密码子的多态性极大地影响了沙特阿拉伯阿拉伯人群中患者的药物反应。

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