Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Shuaifuyuan, Wangfujing, Beijing, 100730, China.
Sci Rep. 2023 May 15;13(1):7849. doi: 10.1038/s41598-023-34200-0.
To better clarify the causal effects between matrix metalloproteinases (MMPs) and estrogen-receptor (ER)-negative breast cancer (BC), we investigated the bidirectional causal relationship between MMPs and ER-negative BC by mendelian randomization (MR) analysis. Summary statistic data of five MMPs were extracted from European participants in 13 cohorts. Data of ER-negative BC collected from one of genome-wide association studies of European ancestry was used as experimental datasets and another four ER-negative BC datasets were used as validation sets. Inverse variance weighted method was used for main MR analysis and sensitivity analysis was also conducted. Serum level of MMP-1 has negative effect on ER-negative BC (odds ratio = 0.92, P = 0.0008) but the latter one was not the cause of the former one, which was supported by validation sets. No bidirectional causal effect was detected between the other four types of MMPs and ER-negative BC (P > 0.05). Sensitivity analysis indicated robustness of the above results without remarkable bias. To conclude, serum MMP-1 may be a protective factor against ER-negative BC. No reciprocal causality was found between the other kinds of MMPs and ER-negative BC. MMP-1 was indicated as a biomarker for risk of ER-negative BC.
为了更好地阐明基质金属蛋白酶（MMPs）与雌激素受体（ER）阴性乳腺癌（BC）之间的因果关系，我们通过孟德尔随机化（MR）分析研究了 MMPs 与 ER 阴性 BC 之间的双向因果关系。从 13 个队列的欧洲参与者中提取了五组 MMP 的汇总统计数据。从一个全基因组关联研究的欧洲裔人群中收集到的 ER 阴性 BC 数据被用作实验数据集，另外四个 ER 阴性 BC 数据集被用作验证集。主要 MR 分析采用了逆方差加权法，还进行了敏感性分析。MMP-1 的血清水平对 ER 阴性 BC 有负面影响（比值比=0.92，P=0.0008），但后者不是前者的原因，这一结果在验证集中得到了支持。其他四种类型的 MMPs 与 ER 阴性 BC 之间没有检测到双向因果关系（P>0.05）。敏感性分析表明，上述结果没有明显偏差，具有稳健性。总之，血清 MMP-1 可能是 ER 阴性 BC 的保护因素。其他类型的 MMPs 与 ER 阴性 BC 之间没有相互的因果关系。MMP-1 被认为是 ER 阴性 BC 风险的生物标志物。
