散发性大肠腺癌易感性与谷胱甘肽转硫酶P1基因型的关系.docVIP

散发性大肠腺癌易感性与谷胱甘肽转硫酶P1基因型的关系 【摘要】 　　目的 探讨 中国 汉族人群散发性大肠癌(SCRAC)易感性与谷胱甘肽转硫酶(GST)P1基因型的关系。方法 采用聚合酶链反应技术(PCR)检测108例大肠癌患者和120例健康人群的GSTP1基因型，采用χ2检验，分析比较GSTP1基因型频率在SCRAC组和健康对照组之间的分布差异。 结果 GSTP1基因VaL/VaL基因型频率在SCRAC组中明显增高，与对照组相比，有显著性差异(43.5%vs30.8%,P=0.002,OR=0.430,95%CI:0.250～0.739)；根据临床特征对SCRAC组进行分层分析，发现VaL/VaL基因型与SCRAC病变部位无关(P0.05)，但在Dukes C期和低分化SCRAC患者中分布频率均明显增高(P0.05)。结论 GSTP1基因型与中国汉族人群SCRAC的易感性相关。 【关键词】 谷胱甘肽转硫酶P1 基因型 散发性大肠癌 易感性 　　【Abstract】 Objective To investigate the relationship between the genotype of glutathione S-transferase P1 and the susceptibility to sporadic colorectal adenocarcinoma(SCRAC) in Chinese Hans. Methods Polymerase chain reaction(PCR) was used in the study of GSTP1 genotype, then the discrepancies of GSTP1 genotype frequencies were analysed between 108 SCRAC patients and 120 healthy controls by χ2 test. Results The frequency of VaL/VaL genotype was higher in the SCRAC patients than that in the controls (43.5%vs30.8%,P=0.002,OR=0.430,95%CI:0.250～0.739).To stratificate the SCRAC patients by clinical features, we found there were no association between the frequency of VaL/VaL genotype and the location of SCRAC (P0.05).However, the VaL/VaL genotype of GSTP1 was significantly associated with colorectal adenocarcinoma of Dukes C classification (χ2=7.380,P=0.007,OR=0.347,95%CI:0.160～0.753 ) and poor differentiation (χ2=11.213,P=0.001,OR=0.270,95%CI:0.124～0.590 ), respectively. Conclusions The GSTP1 genotype is strongly correlated with the susceptibility to sporadic colorectal adenocarcinoma in Chinese Hans. 　　【Key words】 Glutathione S-transferase P1 Genotype Sporadic colorectal adenocarcinoma Susceptibility 　　 　　谷胱甘肽转硫酶(glutathione S-transferase ,GST) 在人体中广泛存在，尤其在生殖腺、肝脏及结肠中较高表达,属体内重要的Ⅱ相代谢酶。GST能催化相代谢过程所产生的多种致癌物质与谷胱甘肽(GSH)巯基(-SH)共轭结合，形成亲水性物质排出体外，从而影响机体对毒性物质的解毒作用。GSTP1属GST家族重要成员，该基因第303位点碱基发生A→G突变后，其105密码子异亮氨酸被缬氨酸取代，可引起GSTP1酶活性下降，机体对多种毒性物质降解能力下降，导致肺癌、膀胱癌等多种肿瘤危险性增加［１，２］。散发性大肠癌(SCRAC)发病机制主要涉及环境和遗传两方面，而环境因素致癌在很大程度上取决于个体发生肿瘤的易感性。毒物代谢酶的基因多态现象是肿瘤遗传易感性的重要方面。本