吸烟和细胞色素P4501A1-MspⅠ、谷胱甘肽硫转移酶T1基因多态性与口腔癌的相关性研究

Correlation between smoking and the polymorphisms of cytochrome P450 1A1-MspⅠand glutathione S-transferase T1 genes and oral cancer

目的探讨吸烟和细胞色素P450（CYP）1A1-MspⅠ、谷胱甘肽硫转移酶（GST）T1基因多态性与口腔癌发病之间的关系。方法采用病例-对照研究的方法,以300例口腔癌患者（病例组）及300例非癌对照者（对照组）的外周血白细胞为样本,利用聚合酶链反应（PCR）技术检测Ⅰ相代谢酶CYP1A1-MspⅠ和Ⅱ相代谢酶GSTT1基因多态性,并分析吸烟和2种代谢酶基因多态性与口腔癌的相关性。结果病例组CYP1A1-MspⅠ突变纯合型（m2/m2）和GSTT1基因缺陷型[GSTT1（-）]的频率分布分别为38.33%、69.33%,而对照组的频率分布分别为21.00%、44.33%,二者差异有统计学意义（P〈0.01）。CYP1A1-MspⅠ（m2/m2）者患口腔癌的风险显著增加（OR=2.34,95%CI为1.76~4.07）。GSTT1（-）者患口腔癌的风险也显著增加（OR=2.84,95%CI为1.98~4.54）。基因突变的协同分析发现CYP1A1-MspⅠ（m2/m2）/GSTT1（-）在病例组和对照组中的分布频率分别为30.67%和6.67%,二者差异有统计学意义（P〈0.01）。CYP1A1-MspⅠ（m2/m2）/GSTT1（-）者患口腔癌的风险显著增加（OR=8.27,95%CI为3.63~11.29）。病例组的吸烟率显著高于对照组的吸烟率（OR=2.71,95%CI为1.31~4.52,P〈0.01）,CYP1A1-MspⅠ（m2/m2）及GSTT1（-）与吸烟有协同作用（OR=25.00,95%CI为11.87~35.64）。结论 CYP1A1-MspⅠ（m2/m2）和GSTT1（-）是口腔癌的易感因素,吸烟与口腔癌的易感性也有关,CYP1A1-MspⅠ（m2/m2）和GSTT1（-）与吸烟在口腔癌的发生上有相互促进的作用。

Objective To investigate the correlation between the combination of smoking and the polymorphisms of cytochrome P450（CYP） 1A1-MspⅠ and glutathione S-transferase（GST） T1 genes and oral cancer.Methods The genetic polymorphisms of CYP1A1-MspⅠ and GSTT1 were detected by polymerase chain reaction（PCR） technique in peripheral blood leukocytes of 300 oral cancer cases and 300 non-cancer controls,and the correlation between smo-king,the two metabolic enzymes genetic polymorphisms and oral cancer were analyzed.Results The frequencies of CYP1A1-MspⅠ（m2/m2） and GSTT1（-） were 38.33% and 69.33% in oral cancer cases and 21.00% and 44.33% in healthy controls respectively.Statistical tests showed significant difference in the frequencies between the two groups（P0.01）.The risk of oral cancer with CYP1A1-MspⅠ（m2/m2） was significantly higher than that of controls（OR= 2.34,95%CI 1.76-4.07）.The individuals who carried with GSTT1（-） had a high risk of oral cancer（OR=2.84,95%CI 1.98-4.54）.Combined analysis of the polymorphisms showed that percentage of CYP1A1-MspⅠ（m2/m2）/GSTT1（-） in oral cancer and control groups was 30.67% and 6.67% respectively（P0.01）.The people who carried with CYP1A1MspⅠ（m2/m2）/GSTT1（-） had a high risk of oral cancer（OR=8.27,95%CI 3.63-11.29）.The smoking rate of the case group was significantly higher than that in the control group（OR=2.71,95%CI 1.31-4.52,P0.01）,and statistic analysis suggested an interaction between smoking and CYP1A1-MspⅠ（m2/m2）/GSTT1（-） genotypes polymorphisms which increased risk of oral cancer（OR=25.00,95%CI 11.8735.64）.Conclusion CYP1A1-MspⅠ（m2/m2） and GSTT1（-） are the risk factors in oral cancer.Smoking is also related to the susceptibility to oral cancer.There may be a synergetic interaction among CYP1A1-MspⅠ（m2/m2）,GSTT1（-） and smoking on the elevated susceptibility of oral cancer.