【作者】 谭聪；

【导师】 金永堂；

【作者基本信息】 浙江大学 ， 劳动卫生与环境卫生学， 2012， 硕士

【摘要】 目的研究P53基因突变、RARβ基因甲基化与肺癌临床病理类型的关系,探讨肺癌发病过程中P53突变与RARβ甲基化的相互关系。方法采用单纯病例研究方法,收集198例原发性肺癌患者术中切除的新鲜癌组织标本,并应用PCR产物直接测序及甲基化特异性PCR法分别检测其P53基因第5～9外显子突变及RARβ基因启动子CpG岛甲基化状况,结合患者问卷资料进行χ2检验及多因素logistic回归分析。结果P53突变及RARβ甲基化检出率分别为36.4%和58.1%。吸烟患者P53突变及RARβ甲基化的危险性增加,OR值分别为2.41及2.26；有肺癌家族史的病例P53突变的危险性减小,OR值为0.26,均有统计学意义(P<0.05)。吸烟、P53突变且吸烟使患鳞癌的危险性增加,OR值分别是3.01和4.29；RARβ甲基化使患周围型肺癌危险性增加,OR值为1.95；RARβ甲基化、RARβ甲基化且P53突变使患Ⅱ期及以上肺癌危险性增加,OR值分别是2.13和3.06(P值均<0.05)。RARβ甲基化癌组织P53G:C→T:A突变率及突变构成比均高于RARβ非甲基化癌组织,差异有统计学意义(P值均<0.05)。P53G:C→T:A型突变使检出RARβ甲基化的危险性增加,OR值为3.22；在吸烟和肺鳞癌患者中,该危险性分别增加至3.65及4.71倍(P值均<0.05)。结论P53突变、RARβ甲基化及吸烟与肺癌临床病理类型密切相关；肺癌发病过程中RARβ甲基化与P53G:C→T:A型突变有关。更多还原

【Abstract】 Objective To investigate the relationship between P53mutation, RARβmethylation and the clinical and pathological type of lung cancer, and to explore the relationship between P53mutation and RARβ methylation in lung carcinogenisis. Methods Using case-only study, collected samples of fresh cancer tissue from198primary lung cancer patients during the resection surgery, detected their mutation status of exons5through9in P53gene and methylation status of CpG islands in the promoter of RARβ gene by direct sequencing of PCR products and methylation-specific PCR respectively, and analyzed the result with questionnaire data by chi-square test and logistic regression analysis. Results P53mutation and RARβ methylation were detected in36.4%and58.1%tumors respectively. Patients with smoking history had an increased risk of both P53mutation and RARβ methylation with OR of2.41and2.26and cases with family history of lung cancer had a decreased risk of P53mutation with OR of0.26(all P<0.05). Both Smoking and P53mutation with smoking history increased the risk of squamous cell carcinoma, OR values were3.01and4.29, respectively; RARβ methylation increased the risk of peripheral lung cancer with OR of1.95; Both RARβ methylation and RARβ methylation with P53mutation increased the risk of advanced lung cancer, OR values were2.13and3.06respectively (all P<0.05). Compared with tumors with unmethylated RARβ, P53G:C→T:A mutation rate and mutation proportions were higher in tumors with RARβ methylation with statistically significant (all P<O.05). P53G:C→T:A mutations increased the risk of detecting RARβ methylation with OR of3.22, and the risk increased to3.65and4.71fold in patients with smoking history and in cases with squamous cell carcinoma respectively (all P<0.05). Conclusion P53mutation, RARβ methylation and smoking were closely related to the clinical and pathological type of lung cancer. RARfβ methylation was associated with P53G:C→T:A mutations during the lung cancer pathogenesis.更多还原