Mitogen/Extracellular Signal-Regulated Kinase Kinase-5 Promoter Region Polymorphisms Affect the Risk of Sporadic Colorectal Cancer in a Southern Chinese Population
Mitogen/Extracellular Signal-Regulated Kinase Kinase-5 Promoter Region Polymorphisms Affect the Risk of Sporadic Colorectal Cancer in a Southern Chinese Population
复制标题
丝裂原/细胞外信号调节激酶激酶 5 启动子区多态性影响中国南方人群散发性结直肠癌的风险
DOI：
10.1089/dna.2011.1232
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发表时间：
2012-03-01
影响因子：
3.1
通讯作者：
Wang, Jianping
中科院分区：
文献类型：
--
作者：
Diao, Dechang;Wang, Lei;Wang, Jianping
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.
