Zubor Pavol, Lasabova Zora, Hatok Jozef, Stanclova Andrea, Danko Jan
Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University, 03659 Martin, Slovak Republic.
Oncol Rep. 2007 Jul;18(1):211-7.
The human multidrug resistance gene 1 (MDR-1) encodes a plasma membrane P-glycoprotein (P-gp) that functions as the transmembrane efflux pump for various structurally unrelated anticancer agents and toxins. Polymorphisms in the MDR-1 gene may have an impact on the expression and function of P-gp, thereby influencing the susceptibility to various diseases, including cancer. We investigated the incidence of C3435T polymorphisms at exon 26 in the MDR-1 gene in 92 women with breast cancer and potential association of altered genotypes with smoking and high body mass index in cancer development among patients. The MDR-1C3435T allelotype and genotype analysis revealed a high incidence (75.0%) of polymorph alteration in the MDR-1 gene. The frequencies of homozygous T/T, heterozygous C/T and homozygous C/C genotypes were 25.0, 50.0 and 25.0%, respectively. The risk of breast carcinoma in patients with MDR-1 polymorphism was significantly associated with the higher body mass index, where women with BMI >30 kg/m(2) and C allele in genotype had a higher risk of disease compared to patients with lower amounts of body fat tissue (p=0.0439). The risk was highest for the homozygous carriers of C allele with BMI >30 kg/m(2) compared to patients with BMI 25.1-30 or <or=25 kg/m(2) (OR 3.65, 95% CI 0.94-14.20; or OR 2.50, 95% CI 0.55-11.41), respectively. Consistent with the results of genotyping and BMI analyses, smoking patients harboring the C/T or C/C genotype had an increased risk of cancer (OR 1.28, 95% CI 0.23-7.17; OR 1.58, 95% CI 0.28-10.44, respectively) when exposed to carcinogens in tobacco smoke, although it was not statistically significant. Our findings suggest that the MDR-1C3435T polymorphism occurs in high incidence among women with breast carcinoma where C allele carriers have increased risk of developing cancer when exposed to toxic substances. Our observations are the first that indicate this polymorphism as a modulator of health to be associated with an increased risk of breast cancer.
人类多药耐药基因1（MDR - 1）编码一种质膜P - 糖蛋白（P - gp），它作为多种结构不相关的抗癌药物和毒素的跨膜外排泵发挥作用。MDR - 1基因中的多态性可能会影响P - gp的表达和功能，从而影响包括癌症在内的各种疾病的易感性。我们调查了92例乳腺癌女性患者中MDR - 1基因第26外显子C3435T多态性的发生率以及患者癌症发生过程中基因型改变与吸烟和高体重指数之间的潜在关联。MDR - 1 C3435T等位基因型和基因型分析显示MDR - 1基因中多态性改变的发生率很高（75.0%）。纯合子T/T、杂合子C/T和纯合子C/C基因型的频率分别为25.0%、50.0%和25.0%。MDR - 1基因多态性患者患乳腺癌的风险与较高的体重指数显著相关，与体脂组织量较低的患者相比，基因型为BMI >30 kg/m²且带有C等位基因的女性患癌风险更高（p = 0.0439）。与BMI为25.1 - 30或≤25 kg/m²的患者相比，BMI >30 kg/m²的C等位基因纯合携带者患癌风险最高（分别为OR 3.65，95% CI 0.94 - 14.20；或OR 2.50，95% CI 0.55 - （此处原文有误，应为11.41））。与基因分型和BMI分析结果一致，携带C/T或C/C基因型的吸烟患者在接触烟草烟雾中的致癌物时患癌风险增加（分别为OR 1.28，95% CI 0.23 - 7.17；OR 1.58，95% CI 0.28 - 10.44），尽管差异无统计学意义。我们的研究结果表明，MDR - 1 C3435T多态性在乳腺癌女性中发生率很高，其中C等位基因携带者在接触有毒物质时患癌风险增加。我们的观察结果首次表明这种多态性作为一种健康调节因子与乳腺癌风险增加有关。
