炎症因子与乳腺癌关系的孟德尔随机化研究
Association between inflammatory factors and breast cancer:a Mendelian randomization study
宋文富 1关徐涛 1王冰 2孙士玲 1李盈盈1
作者信息
- 1. 河南中医药大学第一附属医院血液肿瘤科,河南 郑州 450000;河南中医药大学第一临床医学院,河南 郑州 450000
- 2. 河南中医药大学第一附属医院血液肿瘤科,河南 郑州 450000
- 折叠
摘要
目的 采用两样本孟德尔随机化(MR)方法探究炎症因子与乳腺癌的因果关系,为乳腺癌防治提供依据.方法 通过公开数据库收集91种炎症因子(n=14 824)和5种乳腺癌亚型(n=247 173)的全基因组关联研究(GWAS)数据,选取与91种炎症因子相关的单核苷酸多态性(SNP)位点为工具变量.以炎症因子为暴露,乳腺癌为结局,采用逆方差加权法进行MR分析.采用FDR校正降低Ⅰ类错误风险和多重检验的影响.采用Steiger方向检验、MR-Egger回归法、MR-PRESSO检验和留一法验证结果的稳定性和可靠性.结果 β神经生长因子、白介素-5、胱抑素D和C-X-C基序趋化因子1等23种炎症因子与乳腺癌存在统计学关联(均P<0.05);经FDR校正后,仅发现抑瘤素M丰度升高与Basal-like(三阴性)乳腺癌发病风险增加存在统计学关联(OR=1.186,95%CI:1.081～1.302,P=0.001,q=0.029),其他22种炎症因子与乳腺癌的关联发生Ⅰ类错误的风险较高(均q＞0.1).敏感性分析显示结果稳健,未发现对结果有强影响的工具变量,可排除异质性、水平多效性和反向因果对该结果产生的影响.结论 抑瘤素M丰度升高可能增加Basal-like(三阴性)乳腺癌发病风险.
Abstract
Objective To examine the causal relationship between inflammatory factors and breast cancer using two-sam-ple Mendelian randomization(MR)approach,so as to provide the basis for the prevention and treatment of breast can-cer.Methods Data of 91 inflammatory cytokines(n=14 824)and 5 subtypes of breast cancer(n=247 173)were collect-ed from genome-wide association studies(GWAS).Single nucleotide polymorphism(SNP)associated with 91 inflammato-ry factors were selected as instrumental variables.MR analyses were performed using the inverse-variance weighted(IVW)method with inflammatory factors as exposure factors and breast cancer as outcome variables.The risk of type Ⅰ error and the effect of multiple testing were reduced using the FDR correction method.The stability and reliability of the results were verified using Steiger test of directionality,MR-Egger regression,MR-PRESSO test and leave-one out method.Results Twenty-three inflammatory factors,including β nerve growth factor,interleukin-5,cystatin D and C-X-C chemokine ligand 1 were statistically associated with breast cancer(all P<0.05).After FDR adjustment,only evaluat-ed abundance of oncostatin-M was found to be statistically associated with an increased risk of Basal-like(triple-nega-tive)breast cancer(OR=1.186,95％CI:1.081-1.302,P=0.001,q=0.029),and the other 22 inflammatory factors had a high risk of type Ⅰ error(all q>0.1).The sensitivity analysis indicated that the results were robust.No instrumental vari-ables were found to have a significant impact on the results,which could exclude the influence of heterogeneity,horizon-tal pleiotropy,and reverse causality on the outcome.Conclusion The increased abundance of oncostatin-M may in-crease the risk of Basal-like(triple-negative)breast cancer.
关键词
乳腺癌/炎症因子/抑瘤素M/孟德尔随机化/全基因组关联研究/因果关系Key words
breast cancer/inflammatory factor/oncostatin-M/Mendelian randomization/genome-wide association studies/causal relationship引用本文复制引用
基金项目
河南省教育厅重点科研项目(24A360006)
河南省高等学校青年骨干教师项目(2023GGJS083)
河南省中医药管理局重点项目(2023ZY2004)
河南省中医药管理局重点项目(2023ZY2015)
河南省中医药管理局重点项目(20-21ZY1010)
第七批全国老中医专家学术经验继承工作指导项目(20230522)
河南省青苗人才指导项目(20210411)
出版年
2024
NETL
NSTL
万方数据