DNA修复基因XPD751基因多态性与肺癌化疗敏感性关系的研究  

Polymorphisms in XPD751 gene and sensitivity to platin-based chemotherapy in lung cancer

作　　者：丁忠海[1] 许林[1] 高长明[2] 吴建中[2] 史美祺[3] 冯继锋[3] 

机构地区：[1]南京医科大学附属江苏省肿瘤医院胸外科,江苏南京210009 [2]南京医科大学附属江苏省肿瘤医院流行病研究室,江苏南京210009 [3]南京医科大学附属江苏省肿瘤医院内科,江苏南京210009

出　　处：《中华肿瘤防治杂志》2008年第7期522-525,共4页Chinese Journal of Cancer Prevention and Treatment

基　　金：江苏省科技厅社会发展重点项目(BS2006005);江苏省卫生厅医学科研项目(Z200609)

摘　　要：目的：研究DNA修复基因XPD751基因多态性与肺癌化疗敏感性的关系。方法：收集经病理学确诊的肺癌234例，所有病例化疗前抽静脉血，提取白细胞DNA，用多聚酶链反应-限制性片段长度多态性（PCR—RFLP）分析技术检测XPD751基因型。所有患者均经铂类药物为基础的化疗方案治疗。结果：1）在24例肺癌患者中，XPD751 Lys／Lys、Lys／Gln和Gln／Gln基因型分别为192（82．1％）、40（17．1％）和2（0．8％）例。经化疗后，110例患者有效，总有效率为47．0％。2）XPD75 1Lys／Lys、Lys／Gln和Gln／Gln基因型有效率分别为50．0％（96／192）、30．0％（12／40）和100％（2／2），三者相比差异有统计学意义，Х^2=7．59，P=0．0225。在调整性别、年龄、临床分期、细胞学类型和化疗方案的影响后，发现携带XPD751 Lys／Gln基因型患者化疗失败的可能性是Lys／Lys基因型患者的2．28倍，OR=2．28，95％CI为1．05～4．91。3）携带Lys／Lys基因型患者的恶心呕吐反应和脱发程度均高于Lys／Gln和Gln／Gln基因型患者，Х^2值分别为4．504和4．011，P值分别为0．034和0．045。结论：XPD751基因多态性与肺癌对铂类药物为基础的化疗敏感性相关，检测XPD751基因型可以预测肺癌化疗的敏感性。OBJECTIVE： To investigate the relationship between polyrnorphisms of DNA repair gene XPD751 and sensitivity to plati- num-based chemotherapy in lung cancer. METHODS： A tatal of 234 patients with lung cancer were investigated. All the patients were treated with platinum-based chemotherapy and DNA of peripheral blood leukocytes was obtained before the therapy. XPD751 genotypes were detected by the PCR-RFLP method. RESULTS： 1）Of all cases, the frequencies of XPD751 Lys/Lys,Lys/Gln and Gln/Gln genotype were 82. 1%（192/234）,17. 1%（40/234） and 0. 8%（2/234）, respectively. The overall response rate of platinum-based chemotherapy in all the patients was 47. 0% （110/234）. 2）The response rates of chem- otherapy among patients with XPD751 Lys/Lys, Lys/Gln and Gin/Gin genotype were 50. 0% （96/192） ,30. 0% （12/40） and 100% （2/2）, respectively, being a significant difference, Х^2 = 7. 59, P = 0. 022 5. After adjusting the influencing factors of gender, age, clinical stage, cytology type and chemotherapy regimens,the probability of chemotherapy woke on patients with Lys/Lys genotype 2. 28-fold to that in patients with Lys/Gln genotype, OR= 2.28,95%CI： 1.05 - 4. 91. 3） The incidence rates of vomiting/nausea and alopecie in Lys/Lys genotype were significantly higher than those in the other genotypes,Х^2 =4. 504,P= 0. 034;Х^2 =4. 011,P=0. 045. CONCLUSIONS： The polyrnorphism of XPD751 correlates with the clinical response to platinum-based chemotherapy, and the XPD751 genotypes detected by the PCR-RFLP method can identify lung cancer patients with response to platinum-based chemotherapy.

关 键 词：肺肿瘤/药物疗法 多态现象 遗传 基因 XPD751 药物耐受性 聚酶链反应 

分 类 号：R734.2[医药卫生—肿瘤]