谷胱甘肽S-转移酶M1、T1基因多态与散发性大肠腺癌遗传易感性

目的　探讨谷胱甘肽S 转移酶 (GST)M1、T1基因多态与散发性大肠腺癌 (SCRAC)遗传易感性的关联。方法　应用多重聚合酶链反应 (PCR)技术 ,对经病理组织学确诊的 10 4例SCRAC患者及同期在本院体检的无血缘关系的 10 1例健康人 ,检测其GSTM1和GSTT1基因多态性。结果　 (1)在健康人和SCRAC患者 ,GSTM1、GSTT1空白基因型的频率差异均无显著性 (前者 4 6 5 % :5 6 7% ,χ2 =2 13,P >0 0 5 ;后者 4 7 5 % :6 0 6 % ,χ2 =3 5 2 ,P >0 0 5 )。 (2 )GSTM1空白基因型频率在近端与远端SCRAC患者间、在老年与非老年SCRAC间的频率差异均无显著性 ;而GSTT1空白基因型的频率差异有显著性 (前者 4 4 4 % :6 6 2 % ,χ2 =3 97,P <0 0 5 ;后者 70 9% :4 9 0 % ,χ2 =5 2 1,P <0 0 5 )。 (3)GSTM1、GSTT1均为空白基因联合型的个体患SCRAC的危险性升高 4 33倍 (9 6 % :2 6 9% ,χ2 =7 89,ν =3,P <0 0 5 )。结论　单独的GSTM1或GSTT1空白基因型与SCRAC遗传易感性无关 ,但GSTT1空白基因型与远端SCRAC遗传易感性有关 ,且多见于老年患者。GSTM1、GSTT1均为空白基因的联合基因型是SCRAC的易感基因型。

The relationship between GSTM1, GSTT1 gene polymorphisms and susceptibility to sporadic colorectal adenocarcinoma

OBJECTIVE: To analyse the association genetic polymorphisms of glutathione S-transferase (GST) M1 and T1 with genetic susceptibility to sporadic colorectal adenocarcinoma (SCRAC). METHODS: All subjects are unrelated the Han people in Hubei province of China. Using multiple PCR, we studied the genetic polymorphisms of the GSTM1, GSTT1 genes of 101 healthy controls and 104 SCRAC patients. RESULTS: (1) All the differences of the frequency of GSTM1 null genotype between SCRACs and the controls, between proximal and distal SCRACs and between the elder and the younger SCRACs did not reach statistical significance. (2) The differences of the frequency of GSTT1 null genotype between SCRACs and the controls did not reach statistical significance too; But the null genotype for GSTT1 was significantly more common among distal SCRACs when compared with the proximals (66.2%:44.4%, chi(2) = 3.97, P < 0.05) and more common among the elder SCRACs when compared with younger SCRACs (70.9%:49.0%, chi(2) = 5.21, P < 0.05). (3) Subjects carring both of the null genotypes for GSTM1 and GSTT1 had more than 4.33-fold risk for developing SCRACs compared with the subjects caring both of the nonull genotypes for GSTM1 and GSTT1 (OR = 4.33, 95% confidence interval, 1.56 - 12.04). CONCLUSIONS: (1) There was no association the susceptibility to SCRAC with GSTM1 or GSTT1 null genotype alone, but the date suggests GSTT1 null genotype may influence the distal SCRAC, especially the elder; (2) The individual with both of the null genotypes of GSTM1 and GSTT1 increases markedly the risk of SCRAC, and this genotype is the susceptibility gene to SCRAC.