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

摘要

Objective To investigate the correlation between the combination of smoking and the polymorphisms of cytochrome P450(CYP) lAl-Msp I and glutathione S-transferase (GST) Tl genes and oral cancer. Methods The genetic polymorphisms of CYPIAI-Msjp I 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 smoking, the two metabolic enzymes genetic polymorphisms and oral cancer were analyzed. Results The frequencies of CYP1A1-Msp I (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 (P<0.01). The risk of oral cancer with CYPIAI-Afsp 1 (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 CYPIAI-Msp I (m2/m2)/GSTTl (-) in oral cancer and control groups was 30.67% and 6.67% respectively (P<0.01). The people who carried with CYP1A1-Msp I Gn2/m2)/GSTTl (-) 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, P<0.01), and statistic analysis suggested an interaction between smoking and CYPIAI-Msp I (m2/m2)/GSTTl (-) genotypes polymorphisms whichincreased risk of oral cancer (OR =25.00, 95% CI 11.87-35.64). Conclusion CYPIAI-Msp I (m2/m2) and GS-TT1 (-) are the risk factors in oral cancer. Smoking is also related to the susceptibility to oral cancer. Theremay be a synergetic interaction among CYPIAI-Msp I(m2/M2). GSTTI(-) and smoking on the elevated susceptibilityof oral cancer.%目的 探讨吸烟和细胞色素P450 (CYP) 1A1-Msp Ⅰ、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-Msp Ⅰ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-Msp Ⅰ突变纯合型(m2/m2)和GSTT1基因缺陷型[GSTT1(一)]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-Msp Ⅰ(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(一)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-Msp Ⅰ (m2/m2)/GSTT1(一)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).CYP1A 1-Msp Ⅰ (m2/m2)/GSTT1(一)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-Msp Ⅰ(m2/m2)及GSTT1(一)与吸烟有协同作用(OR=25.00,95％CI为11.87～35.64).结论 CYP1A1-Msp Ⅰ (m2/m2)和GSTT1(一)是口腔癌的易感因素,吸烟与口腔癌的易感性也有关,CYP1A1-Msp Ⅰ (m2/m2)和GSTT1(一)与吸烟在口腔癌的发生上有相互促进的作用.