基质金属蛋白酶13基因多态性与非小细胞肺癌易感性的关联研究  

Assosiation between matrix metalloproteinase 13 gene polymorphism and susceptibility to non-samall cell lung cancer

作　　者：王伟[1] 王智超[2] 刘歆阳[2] 王斌[3] 曾辉[4] 米丽丽[4] 王瑞[4] 

机构地区：[1]河北省成安县人民医院外科,河北邯郸056700 [2]复旦大学上海医学院,上海200032 [3]河北省人民医院肿瘤科,河北石家庄050011 [4]河北医科大学第四医院胸外科,河北石家庄050011

出　　处：《中国现代医学杂志》2013年第1期35-39,共5页China Journal of Modern Medicine

基　　金：河北省普通高等学校强势特色学科肿瘤学建设经费资助项目(No:冀教告[2005]52号);河北省卫生厅医学科学研究重点课题计划项目(No:20100123)

摘　　要：目的探讨基质金属蛋白酶13基因（MMP-13）启动子区-77bpA／G单核苷酸多态性（syP）与我国北方人非小细胞肺癌（NSCLC）遗传易感性的关系。方法采用基于医院的病例-对照研究方法，收集300例非小细胞肺癌患者（其中鳞癌161例，腺癌139例）和300例健康对照个体的静脉抗凝血5mL，以蛋白酶K消化一饱和氯化钠盐析法提取外周血白细胞DNA，采用聚合酶链反应-限制性片段长度多态性方法对MMP～13—77A／GSNP进行基因分型．比较NSCLC病例组与健康对照组之间等位基因及基因型分布。结果NSCLC病例组中吸烟个体的比例（62．00％）明显高于健康对照组（36．30％）（x^2=39．54，P=0．00），经年龄、性别校正后的OR值为3．74（95％CI=2．451～5．705）。健康对照组中的MMP-13基因启动子区转录起始点上游77bp处A／GSNP的基因型分布符合Hady—Weinberg平衡（P〉O．05）。MMP-13基因-77A／G多态性位点的A等位基因频率在病例组为50．33％，显著高于健康对照组的44．33％（x^2=4．332，P〈0．05）。MMP-13基因-77A／GSNP基因型分布在NSCLC病例组和健康对照组之间亦有显著性差异（x^2=8．638，P〈0．05）。与G／G基因型相比，A／A基因型能显著增加NSCLC的发病风险，（OR=1．309，95％CI=1．033-1．659）。根据NSCLC病理类型进行分层分析发现MMP-13基因-77A／GSNP与肺腺癌的发病风险相关；与G／G基因型相比，A／A基因型能够显著增加肺腺癌的发病风险，经年龄、性别和个体吸烟状况校正后的OR值为1．512（95％CI=I．128-2．028）。结论吸烟可以显著增加NSCLC的发病风险。MMP-13基因SNP与NSCLC的发病风险相关，与G／G基因型相比，A／A基因型可显著增加NSCLC尤其是肺腺癌的发病风险。[ Objective] To investigate the associations between -77A/G in the promoter region of MMP-13 gene and susceptibilities of non-small cell lung cancer （NSCLC） in North China. [ Methods ] This hospital-based case-control study included 300 non-small cell lung cancer patients （161 with squamous carcinoma and 139 with adenocarcinoma） and 300 healthy controls. Genomic DNA was extracted by using proteinase K digestion followed by a salting out procedure. Polymorphisms of MMP-13 gene were analyzed by PCR-restriction fragment length polymor- phism （RFLP）. [ Results ] The frequency of smokers in NSCLC patients （62.00%） was significantly higher than that in healthy controls （36.30%） （x^2=39.54, P =0.00）. Smoking may increase the risk of developing NSCLC（age and gen- der adjusted OR=3.74, 95% CI=2.451-5.705）. The distribution of MMP-13-77A/G SNP in the promoter region genotypes among healthy controls did not significantly deviate from that expected by Hardy -Weinberg equilibrium （P 〉0.05）. Frequency of the A allele in NSCLC patients was 50.33%, which was significantly higher than that in healthy controls 44.33% （x^2=4.332, P〈0.05）. The genotype distribution of the MMP-13-77A/G SNP in the overall NSCLC patients was also significantly different from that in healthy controls （x^2=8.638, P =0.013）. Compared with G/ G genotype, the A/A genotype increased the risk of NSCLC （age, gender and smoking status adjusted OR=1.309, 95% CI=1.033~1.659）. Stratification analysis according to histological type, MMP-13-77A/G SNP in the promoter region showed significant statistical influence on the risk of adenocarcinoma. And comparing with G/G genotype, the A/A genotype could increase the risk of adenocarcinoma （age, gender and smoking status adjusted OR=1.512, 95% CI=1.128-2.028）. [ Conclusions ] Smoking may increase the risk of drveloping NSCLC. The allele type and geno- type distribution of the MMP-13-77A/G SNP in the overall NSCLC patients was significantly different from that in healthy

关 键 词：非小细胞肺癌 基质金属蛋白酶基因 多态性 单核苷酸 易感性 

分 类 号：R730.231[医药卫生—肿瘤]