文章：

卵巢癌中BRCA突变位置与生存结局关联性的系统评价与荟萃分析

Survival Outcomes Associated with the Location of BRCA Mutations in Ovarian Cancer: A Systematic Review and Meta-Analysis

原文发布日期：14 May 2025

DOI: 10.3390/cancers17101661

类型: Article

开放获取: 是

英文摘要：

Background/Objective:BRCA1andBRCA2genes contain functional domains that operate at different stages of the DNA damage response. Although studies have suggested that the location ofBRCA1/2mutations may influence clinical outcomes, no discernible pattern has been observed indicating which mutation location influences clinical outcomes in patients with ovarian cancer withBRCA1/2mutations. Therefore, this study aimed to evaluate the differences in survival outcomes betweenBRCA1/2mutation locations, with a specific focus on exon 11, in patients with epithelial ovarian cancer. Methods: A comprehensive literature review was conducted using PubMed, Embase, and Cochrane Library databases, including articles published up to 13 August 2024. Progression-free survival (PFS) and overall survival (OS) were assessed based on theBRCAmutation location, with subgroup analyses focusing on exon 11 mutations inBRCA1andBRCA2.Statistical heterogeneity was evaluated using the I2index. Results: Seven studies involving 1535 patients were included.BRCA2exon 11 mutations demonstrated a significant PFS advantage (HR, 0.586; 95% CI, 0.346–0.994, I2= 55%), whereasBRCA1exon 11 mutations had no significant effect on PFS or OS. Conclusions: These findings suggest differential prognostic outcomes based on theBRCAmutation location, highlighting the clinical relevance ofBRCA2exon 11.BRCA2exon 11 mutations were associated with improved PFS, which underscores the prognostic significance of theBRCAmutation location, particularly exon 11, in ovarian cancer. These findings reinforce the biological relevance of exon 11 by consolidating evidence from multiple studies that suggest potential prognostic implications of mutations within this region.

摘要翻译： 

背景/目的：BRCA1和BRCA2基因包含在DNA损伤应答不同阶段发挥作用的功能结构域。尽管已有研究表明BRCA1/2突变的位置可能影响临床结局，但尚未观察到明确的模式表明哪种突变位置会影响携带BRCA1/2突变的卵巢癌患者的临床结局。因此，本研究旨在评估BRCA1/2突变位置（特别关注第11外显子）在上皮性卵巢癌患者生存结局方面的差异。方法：通过PubMed、Embase和Cochrane Library数据库进行了全面的文献综述，纳入截至2024年8月13日发表的文章。根据BRCA突变位置评估无进展生存期（PFS）和总生存期（OS），并针对BRCA1和BRCA2的第11外显子突变进行了亚组分析。使用I²指数评估统计异质性。结果：共纳入7项研究，涉及1535名患者。BRCA2第11外显子突变显示出显著的PFS优势（HR, 0.586; 95% CI, 0.346–0.994, I²= 55%），而BRCA1第11外显子突变对PFS或OS均无显著影响。结论：这些发现表明，基于BRCA突变位置存在不同的预后结局，突显了BRCA2第11外显子的临床相关性。BRCA2第11外显子突变与改善的PFS相关，这强调了BRCA突变位置（特别是第11外显子）在卵巢癌中的预后意义。这些发现通过整合多项研究的证据，强化了第11外显子的生物学相关性，表明该区域内的突变可能具有潜在的预后影响。

原文链接：

Survival Outcomes Associated with the Location of BRCA Mutations in Ovarian Cancer: A Systematic Review and Meta-Analysis