α_1抗胰蛋白酶基因多态性与肺癌易感性的研究

Relationship between α_1 AT Polymorphism and Lung Cancer Susceptibility

目的研究高海拔地区人群中α1抗胰蛋白酶基因多态性与肺癌易感性的关系。方法采集甘肃省兰州市人群血标本330例,包括肺癌组130例,COPD组100例,对照组100例。采用PCR-RFLP技术,筛查α1AT基因外显子Ⅴ、Ⅲ及3'端突变体出现的频率,分析其与肺癌的关系。结果检测到α1AT的Z、S基因型存在,但在3组中分布差异无统计学意义;非小细胞肺癌组发现3'端突变体(3m型基因)18例(13.8%),COPD组8例(8%),均明显高于对照组,统计学分析显示肺癌组、COPD组与对照组之间3m型基因分布差异有统计学意义(P=0.002);将肺癌组进一步分组分析发现肺癌合并COPD组3'端突变体出现率24%,远高于肺癌不合并COPD组(7.5%);3m型基因阳性患者罹患NSCLC合并COPD的OR值为3.895。结论α1AT的Z、S基因突变型和甘肃高海拔地区人群COPD及肺癌无明确的相关性,而3'端突变体在COPD和肺癌患者中明显增多,是COPD和肺癌的易感因素。携带3'端突变体的人群患肺癌合并COPD的危险性明显增高,提示α1AT的3'端突变体和甘肃高海拔地区人群中肺癌的易感性相关。

Objective To study the relationship between α1AT polymorphism and lung cancer susceptibility in Gansu high ahitude population. Methods Totally 330 blood samples were collected from Gansu high altitude population including 130 eases with lung cancer,100 eases with COPD and 100 individuals as normal control. The frequency of exon V, III and 3＇mutants of α1AT was screened by PCR - RFLP to analyze the correlation of these mutants with lung eancer statistically. Results Although there was no significant differ- ence between the three groups statistically,Z and S alleles were reliably detected in Gansu high altitude population. 3＇mutant was found in 18 patients with NSCLC （13.8%） and 8 patients with COPD （8%） and the frequency of detection was significantly higher than that in control. The prevalence of 3＇mutant in patients of lung eaneer with COPD （24%） was significantly higher than that in patients of lung cancer without COPD （7.5%） with a 3. 895 of odds ratio. Conclusion Based on the results of our study, Z and S alleles were not proved to be relate to the development of COPD and lung cancer yet. However, the frequency of 3＇mutant was higher in the patients with lung cancer or COPD. It indicated that 3＇mutant might be a risk factor of COPD and lung cancer. It also found that the risk of lung cancer complicated with COPD was significantly increased in population earring 3＇mutant. It strongly indicated 3＇mutant might be related to the susceptibility of lung cancer in Gansu high altitude population.