在保加利亚患者中，MDR1（ABCB1）2677G>T和3435C>T多态性与散发性结直肠癌之间无关联。
No association between MDR1 (ABCB1) 2677G>T and 3435C>T polymorphism and sporadic colorectal cancer among Bulgarian patients.
作者信息
Petrova Darinka Todorova, Nedeva Petya, Maslyankov Svilen, Toshev Svetoslav, Yaramov Nikolay, Atanasova Srebrena, Toncheva Draga, Oellerich Michael, von Ahsen Nicolas
机构信息
Department of Medical Genetics, Medical University Sofia, 2, Zdrave Str., 1431 Sofia, Bulgaria.
出版信息
J Cancer Res Clin Oncol. 2008 Mar;134(3):317-22. doi: 10.1007/s00432-007-0279-9. Epub 2007 Aug 3.
PURPOSE
Variation in genetic factors together with xenobiotic exposure may result in increased risk of colorectal cancer. The P-glycoprotein (P-gp) is highly expressed in the apical membrane of enterocytes, where it pumps xenobiotics from the enterocytes back into the intestinal lumen. Thus, polymorphisms that reduce the activity of the MDR1 (ABCB1) efflux pump are potential risk factors for colorectal carcinogenesis. The aim of the present study is to genotype the MDR1 2677G>T (rs2032582) and 3435C>T (rs1045642) polymorphism in patients with colorectal cancer and controls and to identify a possible association between individual genetic variation and susceptibility to colorectal cancer.
METHODS
In the present study, 146 Bulgarian patients with sporadic colorectal cancer and 160 healthy Bulgarian volunteers were evaluated for the two polymorphisms in MDR1. Polymorphisms were identified using rapid-cycle real-time amplification with allele-specific probes and subsequent melting curve analyses on a LightCyclertrade mark (Roche Diagnostics, Mannheim, Germany).
RESULTS
No differences were found between the frequencies of the two mutant alleles in the tumor tissue from the cases and lymphocytes from the controls [frequencies of 2677T: 43.5% in patients and 44.1% in controls; frequencies of 3435T: 48.3% in patients and 50.9% in controls (both P > 0.05)]. The MDR1 polymorphic sequence of the tumor tissue always matched that of normal intestinal tissue from the same patient. Consequently, genotyping of DNA from archived tumor tissues is a valid alternative to the use of leukocyte DNA.
CONCLUSIONS
The present study suggests that MDR1 2677G>T and 3435C>T polymorphism is not a risk factor for sporadic colon cancer among Bulgarians and that somatic mutation at these sites is not involved in the genesis of colon tumors. Further examination using larger number of samples must be necessary to reach to more reliable conclusions.
目的
遗传因素的变异与外源性物质暴露共同作用可能会增加患结直肠癌的风险。P-糖蛋白（P-gp）在肠细胞的顶端膜中高度表达，它可将外源性物质从肠细胞泵回肠腔。因此，降低多药耐药蛋白1（MDR1，ABCB1）外排泵活性的多态性是结直肠癌发生的潜在危险因素。本研究的目的是对结直肠癌患者和对照组进行MDR1 2677G>T（rs2032582）和3435C>T（rs1045642）多态性基因分型，并确定个体基因变异与结直肠癌易感性之间的可能关联。
方法
在本研究中，对146例保加利亚散发性结直肠癌患者和160名健康保加利亚志愿者进行了MDR1的两种多态性评估。使用等位基因特异性探针的快速循环实时扩增及随后在LightCycler商标（德国曼海姆罗氏诊断公司）上进行熔解曲线分析来鉴定多态性。
结果
病例组肿瘤组织中的两个突变等位基因频率与对照组淋巴细胞中的频率之间未发现差异[（2677T频率：患者为43.5%，对照组为44.1%；3435T频率：患者为48.3%，对照组为50.9%（均P>0.05）]。肿瘤组织的MDR1多态性序列始终与同一患者正常肠组织的序列匹配。因此，存档肿瘤组织DNA的基因分型是使用白细胞DNA的有效替代方法。
结论
本研究表明，MDR1 2677G>T和3435C>T多态性不是保加利亚人散发性结肠癌的危险因素，且这些位点的体细胞突变不参与结肠肿瘤的发生。必须进行更多样本的进一步检查才能得出更可靠的结论。
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