乳腺癌患者的多药耐药基因1（MDR1）C3435T多态性

MDR1 C3435T polymorphism in patients with breast cancer.

作者信息

Turgut Sebahat, Yaren Arzu, Kursunluoglu Raziye, Turgut Günfer

机构信息

Department of Physiology, Faculty of Medicine, University of Pamukkale, Denizli, Turkey.

出版信息

Arch Med Res. 2007 Jul;38(5):539-44. doi: 10.1016/j.arcmed.2007.02.005. Epub 2007 Apr 26.

DOI:10.1016/j.arcmed.2007.02.005

PMID:17560460

Abstract

BACKGROUND

The human multidrug-resistant gene (MDR1) encodes P-glycoprotein (Pgp), a membrane-bound efflux transporter conferring resistance to a number of natural cytotoxic drugs and potentially toxic xenobiotics. Single-nucleotide polymorphisms (SNPs) in MDR1 gene are associated with phenotypic variation in Pgp expression levels of tissue. SNPs may alter the physiological protective role of Pgp and, therefore, influence disease risk.

METHODS

In our study we identified the MDR1 C3435T polymorphism in breast cancer patients (n = 57) and healthy subjects (n = 50). DNA was extracted from peripheral blood samples by standard phenol/chloroform extraction method. Polymerase chain reaction-restriction fragment length polymorphism was used for the detection of C3435T single nucleotide polymorphism.

RESULTS

We obtained CC, CT and TT genotype frequencies in breast cancer patients as 12.3%, 57.9% and 29.8%, respectively. In the control group, frequencies of genotypes were found as 36% for CC, 46% for CT and 18% for TT. We observed difference in SNPs in MDR1 gene C3435T polymorphism between breast cancer patients and healthy controls (chi(2) = 8.66, df = 2, p = 0.013). The C allele frequency was found in 41.2% and the T allele frequency was found in 58.8%. C3435T MDR1 gene allele frequencies in breast cancer patients as compared to results in control group were as follows: [OR = 1.5 (95% CI: 1.09-1.96)]. In the patient group, T allele frequency was significantly higher than controls (p <0.01). Clinicopathological parameters of patients with breast cancer were compared for C3435T polymorphism. We did not find any significant difference between clinicopathological parameters and MDR1 phenotype of breast cancer patients. The progression-free survival rate in a subgroup analysis based on MDR1 genotypes with CC genotype was 71.4%, CT genotype was 75.7%, and TT genotype was 88.2%, respectively. This difference was not statistically significant (log rank p = 0.63).

CONCLUSIONS

Results of the present study demonstrated a 1.5-fold increased risk for development of breast cancer in T allele carriers.

摘要

背景

人类多药耐药基因（MDR1）编码P-糖蛋白（Pgp），这是一种膜结合的外排转运蛋白，可赋予对多种天然细胞毒性药物和潜在有毒外源性物质的抗性。MDR1基因中的单核苷酸多态性（SNP）与组织中Pgp表达水平的表型变异相关。SNP可能会改变Pgp的生理保护作用，从而影响疾病风险。

方法

在我们的研究中，我们鉴定了乳腺癌患者（n = 57）和健康受试者（n = 50）中的MDR1 C3435T多态性。通过标准酚/氯仿提取法从外周血样本中提取DNA。采用聚合酶链反应-限制性片段长度多态性方法检测C3435T单核苷酸多态性。

结果

我们在乳腺癌患者中获得的CC、CT和TT基因型频率分别为12.3%、57.9%和29.8%。在对照组中，CC基因型频率为36%，CT基因型频率为46%，TT基因型频率为18%。我们观察到乳腺癌患者和健康对照之间MDR1基因C3435T多态性的SNP存在差异（χ² = 8.66，自由度 = 2，p = 0.013）。发现C等位基因频率为41.2%，T等位基因频率为58.8%。与对照组结果相比，乳腺癌患者中C3435T MDR1基因等位基因频率如下：[比值比（OR）= 1.5（95%可信区间：1.09 - 1.96）]。在患者组中，T等位基因频率显著高于对照组（p <0.01）。比较了乳腺癌患者C3435T多态性的临床病理参数。我们未发现乳腺癌患者的临床病理参数与MDR1表型之间存在任何显著差异。基于MDR1基因型的亚组分析中，CC基因型的无进展生存率为71.4%，CT基因型为75.7%，TT基因型为88.2%。这种差异无统计学意义（对数秩检验p = 0.63）。