P73 G4C14 到 A4T14 多态性与晚期非小细胞肺癌患者的生存相关。

P73 G4C14-to-A4T14 polymorphism is associated with survival in advanced non-small cell lung cancer patients.

机构信息

State Key Laboratory of Genetic Engineering and MOE Key Laboratory of Contemporary Anthropology, School of Life Sciences, Fudan University, Shanghai, China.

Department of Thoracic Surgery, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

出版信息

Thorac Cancer. 2017 Mar;8(2):63-72. doi: 10.1111/1759-7714.12397. Epub 2017 Jan 30.

DOI:10.1111/1759-7714.12397

PMID:28134496

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5334305/

Abstract

BACKGROUND

p73, a structural and functional homolog of p53, plays an important role in modulating cell cycle arrest. This study investigated the association between p73 G4C14-to-A4T14 polymorphism and survival outcomes in a Chinese population of advanced non-small cell lung cancer (NSCLC) patients treated with platinum agents.

METHODS

The p73 G4C14-to-A4T14 polymorphism was genotyped using DNA from blood samples of advanced NSCLC patients (642 in the discovery set and 330 in the replication set). The relationship of the p73 G4C14-to-A4T14 polymorphism with clinical outcomes was analyzed.

RESULTS

Compared with the GC/GC genotype, the genotypes containing AT allele (GC/AT + AT/AT genotypes) were associated with significantly prolonged overall survival (P = 0.040) in the discovery set and after pooling results from the replication set. Stratification analysis revealed that the association was more pronounced in subjects who were older (P = 0.001), male (P = 0.007), smokers (P = 0.006), had a low Eastern Cooperative Oncology Group performance status (P = 0.001), in tumor node metastasis stage IV (P = 0.008), and with adenocarcinoma (P = 0.002). The objective response rates of patients with GC/AT + AT/AT genotypes were statistically higher than those with the GC/GC genotype (P = 0.047).

CONCLUSION

Our findings suggest that the p73 G4C14-to-A4T14 polymorphism may be related to survival outcome in advanced NSCLC patients.

摘要

背景

p73 是 p53 的结构和功能同源物，在调节细胞周期停滞方面发挥重要作用。本研究探讨了中国晚期非小细胞肺癌（NSCLC）铂类药物治疗患者中 p73 G4C14 到 A4T14 多态性与生存结果之间的关系。

方法

使用来自晚期 NSCLC 患者血液样本中的 DNA（发现组 642 例，复制组 330 例）对 p73 G4C14 到 A4T14 多态性进行基因分型。分析 p73 G4C14 到 A4T14 多态性与临床结果的关系。

结果

与 GC/GC 基因型相比，含有 AT 等位基因的基因型（GC/AT + AT/AT 基因型）与发现组和复制组汇总结果中的总生存期显著延长相关（P = 0.040）。分层分析显示，这种相关性在年龄较大的患者（P = 0.001）、男性（P = 0.007）、吸烟者（P = 0.006）、ECOG 表现状态较低（P = 0.001）、肿瘤淋巴结转移 IV 期（P = 0.008）和腺癌患者（P = 0.002）中更为明显。GC/AT + AT/AT 基因型患者的客观缓解率明显高于 GC/GC 基因型患者（P = 0.047）。