首页|炎症因子与乳腺癌关系的孟德尔随机化研究

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

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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.
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.

breast cancerinflammatory factoroncostatin-MMendelian randomizationgenome-wide association studiescausal relationship

宋文富、关徐涛、王冰、孙士玲、李盈盈

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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

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

河南省教育厅重点科研项目河南省高等学校青年骨干教师项目河南省中医药管理局重点项目河南省中医药管理局重点项目河南省中医药管理局重点项目第七批全国老中医专家学术经验继承工作指导项目河南省青苗人才指导项目

24A3600062023GGJS0832023ZY20042023ZY201520-21ZY10102023052220210411

2024

10.19485/j.cnki.issn2096-5087.2024.08.016

预防医学
浙江省预防医学会

预防医学

CSTPCD
影响因子：1.002
ISSN：2096-5087
年,卷(期)：2024.36(8)
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