Guangdong Provincal Hospital of Traditional Chinese Medicine (the postdoctoral mobile research station of Guangzhou University of Traditional Chinese Medicine), Guangdong, China.
DNA Cell Biol. 2012 Mar;31(3):342-9. doi: 10.1089/dna.2011.1232. Epub 2011 Aug 23.
Mitogen/extracellular signal-regulated kinase kinase-5 (MEK5), which belongs to a network of mitogen-activated protein kinase pathways, play a pivotal role in carcinogenesis. The purpose of this study was to investigate whether variants in the MEK5 gene promoter were involved in susceptivity of individuals to sporadic colorectal cancer (CRC). In the present hospital-based case-control study of 737 patients with sporadic CRC and 703 healthy control subjects in a southern Chinese population, the two polymorphisms of MEK5 promoter (i.e., rs7172582C>T and rs3743354T>C) were genotyped by TaqMan assay. There were significant differences between cases and controls in the genotype and allele distribution of the MEK5 gene rs3743354T>C polymorphism. The rs3743354 CC genotype was associated with a significantly decreased risk of CRC when compared with the TT genotype (adjusted odds ratios [ORs]=0.43; 95% confidence interval [CI], 0.24-0.77). Compared to the T allele, a significant correlation was detected between the presence of the C allele and decreased risk of CRC (adjusted OR=0.79; 95% CI, 0.61-0.94). The decreased risk of CRC associated with rs3743354 variant genotypes (i.e., CT+CC) was found in the smoker subgroup (adjusted OR=0.63; 95% CI=0.45-0.88). Further, environmental factors, including smoking and drinking, interacted with rs3743354C variant genotypes to reduce CRC risk. Western blot analysis showed that the levels of MEK5 protein in sporadic CRC neoplastic tissues and adjacent normal colorectal epithelium tissues were lower in the carriers of rs3743354 CC genotypes than that in those with rs3743354 TT genotypes or those with rs3743354 TC genotypes. However, no significant association was found between the rs7172582C>T polymorphism and risk of CRC. These data indicate that the rs3743354 polymorphism in the MEK5 promoter may affect the risk of developing CRC.
丝裂原活化蛋白激酶激酶 5（MEK5）属于丝裂原激活的蛋白激酶途径网络，在致癌作用中发挥关键作用。本研究旨在探讨 MEK5 基因启动子中的变异是否与散发性结直肠癌（CRC）个体的易感性有关。在这项以医院为基础的病例对照研究中，研究人员共纳入了 737 例散发性 CRC 患者和 703 名健康对照者，在南方汉族人群中，采用 TaqMan 法对 MEK5 启动子的两个多态性（即 rs7172582C>T 和 rs3743354T>C）进行了基因分型。MEK5 基因 rs3743354T>C 多态性的基因型和等位基因分布在病例组和对照组之间存在显著差异。与 TT 基因型相比，rs3743354CC 基因型与 CRC 风险显著降低相关（校正比值比[OR] = 0.43；95%置信区间[CI]，0.24-0.77）。与 T 等位基因相比，C 等位基因的存在与 CRC 风险降低显著相关（校正 OR = 0.79；95%CI，0.61-0.94）。在吸烟者亚组中发现，与 rs3743354 变异基因型（即 CT+CC）相关的 CRC 风险降低（校正 OR = 0.63；95%CI = 0.45-0.88）。此外，吸烟和饮酒等环境因素与 rs3743354C 变异基因型相互作用，降低 CRC 风险。Western blot 分析显示，在 rs3743354CC 基因型携带者的散发性 CRC 肿瘤组织和相邻正常结直肠上皮组织中，MEK5 蛋白水平低于 rs3743354TT 基因型或 rs3743354TC 基因型携带者。然而，rs7172582C>T 多态性与 CRC 风险之间没有显著关联。这些数据表明，MEK5 启动子中的 rs3743354 多态性可能影响 CRC 的发病风险。
