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ERCC5 变体与非小细胞肺癌铂类方案治疗结局的相关性:一项前瞻性队列研究。

Variants of ERCC5 and the outcome of platinum-based regimens in non-small cell lung cancer: a prospective cohort study.

机构信息

Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, African Union Organization Street, Abbaseya, Cairo, Egypt.

Department of Clinical Oncology, Faculty of Medicine, Ain Shams University, Abbaseya, Cairo, Egypt.

出版信息

Med Oncol. 2022 Jul 19;39(10):152. doi: 10.1007/s12032-022-01741-9.

Abstract

Excision repair complementary complex 5 (ERCC5) is an important component in the repair pathway of platinum-induced damage. The current study evaluated the effect of ERCC5 variants (rs751402 and rs1047768) on the clinical outcome of platinum-based regimens in non-small cell lung cancer (NSCLC) patients. A prospective, cohort study was conducted on 57 newly diagnosed NSCLC Egyptian patients. Patients received either cisplatin or carboplatin-based chemotherapy. DNA was extracted and the variants were analyzed using real time PCR. This study found no significant difference between the studied variants and patients' response to chemotherapy, progression-free survival (PFS) or overall survival (OS). However, a statistically significant association was found between the histologic subtypes and the studied variants (p = 0.028 and 0.018 for rs751402 and rs1047768, respectively). A statistically significant association was evident between the type of the allele present in the studied polymorphisms, p value = 0.000040. Moreover, the minor allele frequency (MAF) of the studied variants rs751402 and rs1047768 were similar to those of African and European populations, respectively. Results of this study have concluded that ERCC5 variants did not affect the clinical outcome of platinum-based chemotherapy in NSCLC. A significant coinheritance was found between the two variants of ERCC5. Moreover, the similarity between the MAF of the studied variants and the African or European population can guide future research when extrapolating data from African European populations to their Egyptian counterparts.

摘要

切除修复互补基因 5(ERCC5)是铂类诱导损伤修复途径中的重要组成部分。本研究评估了 ERCC5 变体(rs751402 和 rs1047768)对非小细胞肺癌(NSCLC)患者铂类方案临床结局的影响。对 57 例新诊断的埃及 NSCLC 患者进行了前瞻性队列研究。患者接受顺铂或卡铂为基础的化疗。提取 DNA,采用实时 PCR 分析变体。本研究未发现研究变体与患者对化疗的反应、无进展生存期(PFS)或总生存期(OS)之间存在显著差异。然而,在研究变体与组织学亚型之间发现了统计学显著的相关性(rs751402 和 rs1047768 分别为 p=0.028 和 0.018)。在研究的多态性中存在的等位基因类型之间存在统计学显著的相关性,p 值=0.000040。此外,研究变体 rs751402 和 rs1047768 的小等位基因频率(MAF)分别与非洲和欧洲人群相似。本研究的结果表明,ERCC5 变体不影响 NSCLC 铂类化疗的临床结局。ERCC5 的两个变体之间存在显著的共遗传。此外,研究变体的 MAF 与非洲或欧洲人群相似,可指导从非洲-欧洲人群外推数据到埃及人群时的未来研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1aed/9296400/ec66fdd6fd15/12032_2022_1741_Fig1_HTML.jpg

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