Association of combined CYP2E1 gene polymorphism with the risk for esophageal squamous cell carcinoma in Huai'an population, China
Association of combined CYP2E1 gene polymorphism with the risk for esophageal squamous cell carcinoma in Huai'an population, China
复制标题
CYP2E1基因联合多态性与淮安人群食管鳞癌风险的关系
DOI：
10.1097/00029330-200710020-00013
复制
发表时间：
2007-10-20
影响因子：
6.1
通讯作者：
Pu Yue-pu
中科院分区：
文献类型：
--
作者：
Liu Ran;Yin Li-hong;Pu Yue-pu
研究背景细胞色素P450 2 E1（CYP 2 E1）在前致癌物如N-亚硝基胺和其他低相对分子质量有机化合物的代谢活化中起重要作用。本研究旨在探讨CYP 2 E1 Rsal和Dral基因多态性与食管鳞癌易感性的关系，以及CYP 2 E1基因型与mRNA表达水平的相关性。CYP 2 E1基因5 '侧翼区的Rsal多态性和第六内含子的Dral多态性可能影响其转录，采用聚合酶链反应-限制性片段长度多态性技术采用定量真实的-PCR-RFLP技术检测CYP 2 E1 mRNA水平。结果CYP 2 E1基因Rsal、Dral多态性与食管鳞癌易感性无明显相关性（OR=1.67，95%CI：0.89-3.15，P=0.11; OR=1.11，95%CI：0.59-2.09，P=0.74）。SHEsis软件分析表明，Rsal和Dral基因多态性之间不存在连锁不平衡（D '= 0.528，r（2）=0.27）。将Rsal基因多态性与Dral基因多态性结合，发现携带c2等位基因和DD基因型与食管鳞状细胞癌的危险性相关（OR=5.77，95%Cl.）。1.65-20.22）。结论携带c2等位基因和DD基因型的食管鳞癌患者与正常对照组相比，其食管癌基因表达水平无显著性差异，而携带Rsal多态性和Dral多态性的食管鳞癌患者其食管癌基因表达水平与正常对照组相比无显著性差异。基因型c1/c2、D/C及联合等位基因与mRNA表达无显著相关性。
Background Cytochrome P450 2E1 (CYP2E1) has an important role in the metabolic activation of precarcinogens such as N-nitrosoamines and other low relative molecular mass, organic compounds. This study examined whether CYP2E1 Rsal and Dral polymorphism are associated with susceptibility to esophageal squamous cell carcinoma and the correlation between the genotypes and expression levels of CYP2E1 mRNA.Methods Seventy-seven patients with newly diagnosed, untreated esophageal squamous cell carcinoma and 79 healthy controls matched in age, gender and residence were recruited for the control study. An Rsal polymorphism in the 5'-flanking region and a Dral polymorphism in the sixth intron of the CYP2E1 gene, which could possibly affect its transcription, were determined in this study by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and mRNA level of CYP2E1 was measured by quantitative real-time reverse transcription PCR.Results No significant association of Rsal or Dral polymorphism of CYP2E1 with susceptibility of esophageal squamous cell carcinoma were demonstrated (OR=1.67, 95%Cl: 0.89-3.15, P=0.11; OR=1.11, 95%Cl: 0.59-2.09, P=0.74, respectively). With SHEsis software, no linkage disequilibrium was detected between Rsal and Dral polymorphism (D'=0.528, r(2)=0.27). When combined Rsal polymorphism with Dral polymorphism, the association between that carrying c2 allele and DD genotype and the risk for esophageal squamous cell carcinoma were found (OR=5.77, 95%Cl. 1.65-20.22). Compared with the normal controls, the mRNA levels with Rsal polymorphism, Dral polymorphism, or any combined genotypes in cases showed no statistical difference.Conclusions This study suggests that carrying c2 allele and DD genotype conferreded an elevated risk for esophageal squamous cell carcinoma. There was no significant statistical relationship between the genotypes c1/c2, D/C, or the combined allele and mRNA expression.