岭南现代临床外科2024，Vol.24Issue(3)：162-174,13.DOI:10.3969/j.issn.1009-976X.2024.03.004
以孟德尔随机化探究MMPs与乳腺癌的因果关系
Exploring the causal relationship between MMPs and breast cancer risk:a Mendelian random-ization study
韩稚人 1朱祥平 1韩北南 1翁海燕 2杨琼1
作者信息
- 1. 中山大学孙逸仙纪念医院肿瘤内科,广州 510120
- 2. 中山大学孙逸仙纪念医院肿瘤放疗专科,广州 510120
- 折叠
摘要
Abstract
Objective To explore the causal relationships between various subtypes of matrix metallo-proteinases(MMPs)and the risk of developing breast cancer.Methods Using 501 428 genetic variants related to plasma MMPs levels from 990 Europeans in the publicly available MRC-IEU database as instru-mental variables for exposure,and 19 674 639 genetic variants from 201 633 breast cancer patients in the FinnGen version 10 database as instrumental variables for outcome,we conducted a two-sample bidirectional Mendelian randomization analysis.The inverse variance weighted method was used as the primary analysis,with MR-Egger regression,simple mode method,weighted median method,and weighted mode method as secondary complementary regression models.Sensitivity analysis was performed using Cochran's Q test to verify the reliability of the results,MR-Egger test to assess the horizontal pleiotropy of instrumental variables,and leave-one-out analysis to evaluate the potential influence of single nucleo-tide polymorphisms on the results.Results Impact of MMPs on breast cancer:The inverse variance weighted method detected a reverse causal relationship between MMP-7 expression levels and the risk of breast cancer(OR=0.95,95%CI:0.92-0.99,P<0.05);no statistically significant association was found between the expression levels of other MMPs and the risk of breast cancer.Meta-analysis showed no statistically significant association between overall plasma MMPs and the risk of breast cancer.Impact of breast cancer on MMPs:The inverse variance weighted method showed no statistically significant associa-tion between the risk of breast cancer and the expression levels of MMPs.Conclusion The overall effect of MMPs does not have a significant impact on the occurrence and development of breast cancer.However,there is a negative causal relationship between MMP-7 expression levels and the risk of breast cancer.As MMP-7 expression levels decrease,the risk of breast cancer increases.MMP-7 may be a protective factor closely related to the occurrence and progression of breast cancer among MMPs and should be paid more attention.关键词
乳腺癌/MMPs/孟德尔随机化Key words
breast carcinoma/MMPs/mendelian randomization study分类
医药卫生引用本文复制引用
韩稚人,朱祥平,韩北南,翁海燕,杨琼..以孟德尔随机化探究MMPs与乳腺癌的因果关系[J].岭南现代临床外科,2024,24(3):162-174,13.
