散发性大肠腺癌与谷胱甘肽转硫酶M1、T1基因型的关系

Relationship between the susceptibility to sporadic colorectal adenocarcinoma and the genetic polymorphisms of glutathione S-Transferase M1,T1 in Chinese Hans

目的 探讨中国浙江汉族人群散发性大肠腺癌(SCRAC)易感性与谷胱甘肽转硫酶(GST)M1、T1基因型及烟酒嗜好的关系.方法 应用多重聚合酶链反应技术检测118例SCRAC患者和140例健康对照的GSTM1和GSTT1基因型,采用Logistic回归分析GSTM1-、GSTF1-基因型及烟酒嗜好与SCRAC的相关性.结果 GSTM1-和GSTT1-基因型能增加SCRAC的易感性(OR=1.711,95%CI:1.043～2.805;OR=1.734,95% CI:1.057～2.843),而烟酒嗜好对SCRAC的易感性无影响(OR=0.584,95% CI:0.356～0.958;OR=0.378,95% CI:0.217～0.657);根据SCRAC临床特征进一步分层分析,发现GSTM1-和GSTT1-基因型均与年龄因素无关(P＞0.05);GSTM1-基因型在远端SCRAC(P=0.021)、Duke C期SCRAC(P=0.003)及低分化SCRAC(P=0.020)中的分布频率均明显增高;GSTT1-基因型则仅在Duke C期SCRAC中明显增高(P=0.041),而与SCRAC的部位及组织分化程度无关(P＞0.05).另发现GSTM1-/GSTF1-纯合子基因型在SCRAC患者中明显增高(P=0.023).结论 GST基因型与中国浙江汉族人群SCRAC明显相关,GSTM1-和GSTF1-基因型能增加SCRAC的易感性,而烟酒嗜好对SCRAC的易感性无影响.

Objective To investigate the relationship between the genetic polymorphisms of glutathione S-Transferase M1,T1 and the susceptibility to sporadic colorectal adenocarcinoma(SCRAC) and smoking and alcohol consumption in Chinese Hans.Methods Multiplex polymerase chain reaction (M-PCR) was used in the study of genetic polymorphisms of GSTM 1,T1 gene.Logistic analysis was performed to elucidate the roles of GSTM1,GST1,smoking and alcohol.Results The null GSTM1,T1 genotypes could increase the susceptibility to SCRAC(OR=1.711,95% CI:1.043～2.805;OR=1.734,95% CI:1.057～2.843),but smoking and alcohol consumption made no significant effect on SCRAC(OR=0.584,95% CI:0.356～0.958;OR=0.378.95% CI:0.217～0.657).Further stratification of the SCRAC patients by chnical features showed that there were no relationship between the GST M1,T1 genotype and the age of the SCRAC patients.But the frequency of null GSTM1 genotype was significantly associated with distal colon adenocarcinoma (P=0.021),colorectal adenocarcinoma of Dukes C classification (P=0.003) and poor difierentiation (P=0.020),respectively.The frequency of null GSTF1 genotype was only higher in colorectal adenocarcinoma of Dukes C classification(P=0.041).No relationship was found between the location,the degree of differentiation and the frequency of null GSTF1 genotype(P＞0.05).Furthermore,the frequencies of homozygous deletion in GSTM1,T1 genes were found to be significantly increased in SCRAC patients than those in healthy controls(38.9%VS25.7%.P=0.023).Conclusion The GST genotype is strongly correlated with SCRAC incidence in Chinese Hans.The null GSTM1,T1 genotypes can enhance the genetic susceptibility to SCRAC.while smoking and alcohol consumption have no significant effect on the susceptibility to SCRAC.