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晚期非小细胞肺癌对铂类药物的化疗敏感性与p53和p73基因多态的关系
引用本文:Yuan P,Miao XP,Zhang XM,Wang ZH,Tan W,Zhang XR,Sun Y,Xu BH,Lin DX. 晚期非小细胞肺癌对铂类药物的化疗敏感性与p53和p73基因多态的关系[J]. 中华肿瘤杂志, 2006, 28(2): 107-110
作者姓名:Yuan P  Miao XP  Zhang XM  Wang ZH  Tan W  Zhang XR  Sun Y  Xu BH  Lin DX
作者单位:1. 100021,北京,中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院内科
2. 100021,北京,中国医学科学院中国协和医科大学肿瘤研究所病因及癌变研究室
基金项目:国家“十五”攻关项目(2001BA705BI0);首都医学发展科研基金资助项目(2003-2009);北京市科委重大项目(H0209-20030130);教育部博士点基金资助项目(20030023014)
摘    要:目的探讨细胞凋亡相关基因p53和p73的遗传多态,与晚期非小细胞肺癌(NSCLC)对铂类药物化疗敏感性的关系。方法以聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)和突变扩增阻抑系统(ARMS)分析方法,对165例以顺铂(DDP)或卡铂(CBP)为主进行化疗的晚期NSCLC患者,进行p53第72密码子Arg→Pro多态,和p73第2外显子G4C14-A4T14多态的检测,2~3个疗程后进行效果评价。以非条件Logistic回归模型比较不同基因型与化疗疗效的关系。结果携带p53 72Pro等位基因患者的化疗敏感性,是携带p53 72Arg/Arg基因型患者的2、46倍(95%CI,1.11~5.45,P=0.026);而携带至少1个p73突变等位基因(A4T14)的患者,其化疗敏感性是携带p73 G4C14/G4C14基因型患者的2.22倍(95%讲,1.14~4、30,P=0.019)。2个多态位点合并分析结果显示,同时携带p53和p73野生基因型的患者,化疗有效率为7.7%;而携带1个、2个和≥3个p53和p73变异等位基因的患者,化疗有效率分别为34.8%、42.2%和40、7%。结论p53和p73基因遗传多态与晚期NSCLC患者对以铂类药物为主的化疗敏感性有关。

关 键 词:细胞凋亡相关基因 p53 p73 遗传多态 非小细胞肺癌
收稿时间:2004-10-20
修稿时间:2004-10-20

Association of the responsiveness of advanced non-small cell lung cancer to platinum-based chemotherapy with p53 and p73 polymorphisms
Yuan Peng,Miao Xiao-ping,Zhang Xue-mei,Wang Zhong-hua,Tan Wen,Zhang Xiang-ru,Sun Yan,Xu Bing-he,Lin Dong-xin. Association of the responsiveness of advanced non-small cell lung cancer to platinum-based chemotherapy with p53 and p73 polymorphisms[J]. Chinese Journal of Oncology, 2006, 28(2): 107-110
Authors:Yuan Peng  Miao Xiao-ping  Zhang Xue-mei  Wang Zhong-hua  Tan Wen  Zhang Xiang-ru  Sun Yan  Xu Bing-he  Lin Dong-xin
Affiliation:Department of Medical Oncology, Cancer Institute ( Hospital
Abstract:OBJECTIVE: It has been proposed that genetic polymorphisms in apoptosis-related genes might be associated with sensitivity of cancer cells to platinum-based chemotherapy. This study examined the relationship between p53 and p73 genetic polymorphisms and the response to platinum-based chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). METHODS: A total of 165 patients with advanced NSCLC treated with platinum-based chemotherapy were genotyped for the p53 codon 72 Pro-->Arg and p73 exon 2 G4C14-->A4T14 polymorphisms using PCR-RFLP and ARMS-PCR assays. Clinical response to the chemotherapy was obtained after 2 to 3 cycles. The adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using unconditional logistic regression model. All statistical tests were two-sided. RESULTS: The p53 Pro allele carriers had higher response rate than non-carriers (OR = 2.46; 95% CI = 1.11 - 5.45). A higher response rate was also observed for the p73 G4C14/A4T14 or A4T14/A4T14 genotype, compared with the G4C14/G4C14 genotype (OR = 2.22; 95% CI = 1.14 - 4.30). When these two polymorphisms were combined to be analyzed, it was found that the response rate in those carrying the wild-type genotypes at both genes was only 7.7%, whereas the response rates in patients carrying 1, 2, or more than 2 variant alleles of p53 and p73 were 34.8%, 42.2% and 40.7%, respectively. CONCLUSION: Those results suggest that p53 and p73 polymorphisms may be associated with clinical responsiveness to platinum-based chemotherapy in advanced NSCLC.
Keywords:Genetic polymorphisms   p53    p73    Platinum   Non-small cell lung cancer
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