MEK5基因-1118C>T多态性与结直肠癌的关联性研究

Association of MEK5 gene promoter-1118C > T polymorphism with risks of sporadic colorectal cancer

目的:通过实验探讨MAPK信号通路MEK5基因启动子区多态性与结直肠癌(colorectal cancer,CRC)易感性的关系。方法:采用病例对照法,收集737例散发性CRC患者(实验组)及703例健康人(对照组)血液DNA,利用TaqMan-MBG荧光探针法检测MEK5基因启动子区多态性并进行流行病学分析。结果:实验组饮酒和吸烟者比例较对照组明显升高,差异具有统计学意义(P<0.05)。MEK5基因位点-1118C>T等位基因在CRC患者人群与健康对照中分布无统计学差异(P>0.05)。但在BMI≥24kg/m2的肥胖人群中,-1118C>T突变基因型(CT+TT)较野生型CC有增加CRC风险的趋势(OR=1.42,95%CI=0.97～2.08,P>0.05),-1118C>T突变基因型与饮酒和肥胖存在交互作用,使CRC发病风险增加(OR=1.73和1.19;95%CI=1.24～2.42,1.04～1.37,P<0.01,P<0.05)。结论:饮酒和吸烟是散发性CRC发病的独立危险因素,MEK5基因-1118C>T多态性单独与CRC的发病无显著相关性,但其突变基因型(CT+TT)与饮酒和肥胖两个环境因素在增加CRC风险性上存在交互作用,使CRC发病的风险增加。

Objective To investigate the association between promoter -1118C 〉 T polymorphism of MEK5 gene and the susceptibility to sporadic colorectal cancer （CRC）. Methods MEK5 -1118C 〉 T genotypes were determined by Taqman-MBG probes in 703 healthy controls and 737 patients with CRC, and the findings were analyzed epidemiologieally. Results The rates of drinkers and smokers were significantly higher in CRC group than in the control group （P 〈 0.05）. No significant distribution of MEK5 -1118C 〉 T between the patients with CRC cases and the control subjects was observed（P 〉 0.05）. But the genotypes （T ＋ CC） of -1118C 〉 T variants had a trend of increase in the risk of sporadic CRC （OR = 1.42, 95%CI = 0.97 - 2.08, P 〉 0.05）. Further more, the interaction between -1118C 〉 T variant genotypes and fatness （BMI≥24 kg/m2） and drinking increased the risk of CRC （OR = 1.73 and 1.19, 95%CI = 1.24 - 2.42 and 1.04 - 1.37, P 〈 0.01 and 0.05）. Conclusions Drinking and smoking are independent risk factors for sporadic colorectal cancer in southern Chinese population. MEK5 -1118C 〉 T polymorphism has no significant relation with sporadic colorectal cancer, but the interaction between variant genotypes and drinking and fatness is an increased risk of colorectal cancer.