EC-SOD和CYP 1A1-MspⅠ基因多态性及吸烟与口腔癌的相关性研究

Correlation of EC-SOD and CYP 1A1-Msp Ⅰ gene polymorphisms as well as smoking with oral cancer

目的 探讨吸烟和细胞外超氧化物歧化酶（extracellular superoxide dismutase,EC-SOD）、细胞色素P450（cytochrom P450,CYP）1A1-MspⅠ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670例口腔癌患者（病例组）及670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（polymerase chain reaction,PCR）技术检测EC-SOD和CYP1A1-MspⅠ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EC-SOD（C/G）和CYP1A1-MspⅠ突变纯合型（m2/m2）基因频率分布分别为39.40%、68.81%,而对照组的频率分布分别为21.34%、43.88%,二者差异均有统计学意义（P均〈0.05）;EC-SOD（C/G）者患口腔癌的风险显著增加（OR=2.40,95%CI=1.73~4.32）,CYP1A1-MspⅠ（m2/m2）者患口腔癌的风险也显著增加（OR=2.82,95%CI=1.84~4.41）;基因突变的协同分析发现EC-SOD（C/G）/CYP1A1-MspⅠ（m2/m2）在病例组和对照组中的分布频率分别为30.60%和7.16%,差异有统计学意义（P〈0.05）;EC-SOD（C/G）/CYP1A1-MspⅠ（m2/m2）者患口腔癌的风险显著增加（OR=6.87,95%CI=2.18~9.45）;病例组的吸烟率明显高于对照组（P〈0.05）,EC-SOD（C/G）/CYP1A1-MspⅠ（m2/m2）与吸烟有协同作用（OR=44.48,95%CI=17.63~62.07）,EC-SOD（C/G）/CYP1A1-MspⅠ（m2/m2）与吸烟指数（SI〉400）有协同作用（OR=248.81,95%CI=175.46~384.37）。结论 EC-SOD（C/G）和CYP1A1-MspⅠ（m2/m2）是口腔癌的易感因素,吸烟与口腔癌的易感性也有关,EC-SOD（C/G）/CYP1A1-MspⅠ（m2/m2）与吸烟在口腔癌的发生上有协同作用。

Objective To explore the correlation between the smoking, the polymorphisms of extracellular superoxide dis- mutase （EC- SOD） and eytochrom P450 （CYP） 1A1 - Msp I genes and oral cancer. Methods The genetic polymorphisms of EC SOD and CYP1A1 - Msp I were detected by polymerase chain reaction （PCR） technique in peripheral blood leukccytes of 670 oral cancer patients and 670 non- cancer controls, and the correlations between smoking, the genetic polymorphisms of the two metabolic enzymes and oral cancer were analyzed. Results The frequencies of EC- SOD （C/G）and CYPIA1 - Msp I mutation homozygous genotype（m2/m2）were 39.40 % and 68.81% in the oral cancer patients, and 21.34 % and 43.88 % in the healthy controls, both indicating significant differences （P 〈 0.05）. The risk of oral cancer was significantly higher in individuals with EC- SOD （C/G） than in the controls （ OR = 2.40, 95% CI = 1.73 - 4.32）. The individuals carring CYPIA1 - Msp I （m2/m2） also had a higher risk of oral cancer （OR = 2.82, 95 % CI = 1.84- 4.41 ）. Combined analysis of the polymorphisms showed that the frequencies of EC- SOD（C/G）/CYP1A1 - Msp I （m2/m2） in the oral cancer patients and the control group were 30.60 % and 7.16 % respectively, with a statistically significant difference （P〈 0.05 ）. The individuals carrying EC- SOD （C/G）/CYP1A1 - Msp I （m2/m2） had a higher risk of oral cancer （ OR = 6.87, 95 % CI = 2.18 - 9.45）. The smoking rate in the case group was significantly higher than that in the control group （ P 〈 0.05 ）, and statistic analysis indicated a synergetic in- teraction between smoking and EC- SOD（C/G）/CYP1A1 - Msp I （m2/m2） genotype polymorphisms, which more increased the risk of oral caneer （ OR - 44. 48, 95%CI 17.63-62.07）. Smoking index （SI） higher than400 andEC-SOD（C/G）/ CYP1A1 -Msp I （m2/m2） genotype polymorphisms synergetically increased the risk of oral cancer （OR = 248.81, 95% CI-175.46 - 384.37）. Conclusions EC- SOD（C/G） and CYP1A1 - Msp I （m2/m2） are the risk factors for oral cancer. Smok- ing is also related to the susceptibility to oral cancer. There may be synergetic effects among EC- SOD（C/G）/CYP1A1 - Msp I （m2/m2） and smoking on elevating of the susceptibility of oral cancer.