循环炎症蛋白与乳腺癌风险的关系:两样本孟德尔随机化研究  

Circulating Inflammatory Proteins in Relation to Risk of Breast Cancer:A Two-sample Mendelian Randomization Study

作　　者：刘龙娇 姚宇锋 LIU Longjiao;YAO Yufeng(Department of General Surgery,Nanjing Medical University Affiliated Cancer Hospital,Jiangsu Cancer Hospital,Jiangsu Institute of Cancer Research,Nanjing 210000,China)

机构地区：[1]南京医科大学附属肿瘤医院/江苏省肿瘤防治研究所/江苏省肿瘤医院普外科,南京210000

出　　处：《肿瘤防治研究》2024年第5期342-347,共6页Cancer Research on Prevention and Treatment

基　　金：江苏省人社厅“六大高峰人才”(WSN-057)。

摘　　要：目的利用双样本孟德尔随机法研究91种循环炎症蛋白与不同亚型乳腺癌(雌激素受体阳性和阴性乳腺癌)之间的因果关系。方法从全基因组关联研究(GWAS)数据库中提取相应的暴露和结局数据。对数据进行双样本孟德尔随机化分析,以逆方差加权法(IVW)为主要研究方法,MR-Egger、加权中位数、简单模式和加权模式对结果进行补充;并进行敏感性分析验证数据的可靠性。结果IVW结果显示SULT1A1与总BC风险增加相关(P=0.0007);IL-5与总BC风险降低相关(P=0.0011)。SULT1A1(P=0.0011)和CX3CL1(P=0.0005)与ER+BC风险增加相关。Beta-NGF与ER-BC风险增加相关(P=0.0001)。补充分析方法验证研究结果方向、大小均一致。敏感性分析结果表明数据可靠,不存在偏倚。结论通过孟德尔随机化方法,本研究证实了SULT1A1是整体性乳腺癌的危险因素,而IL-5是整体性乳腺癌的保护因素。SULT1A1和CX3CL1是雌激素受体阳性乳腺癌的危险因素,Beta-NGF是雌激素受体阴性乳腺癌的危险因素。Objective To investigate the causal association between 91 kinds of circulating inflammatory proteins and different subtypes of breast cancer(estrogen receptor-positive and-negative breast cancer)using a two-sample Mendelian randomization(MR)method.Methods Corresponding exposure and outcome data were extracted from the genome-wide association study database.The data were analyzed by two-sample MR with inverse-variance weighting(IVW)as the primary study method,and MR-Egger,weighted median,simple mode,and weighted mode were used to complement the results.The results were complemented by sensitivity analysis to verify the reliability of the data.Results The IVW results showed that SULT1A1(P=0.0007)was associated with an increased risk of total BC,whereas IL-5(P=0.0011)was associated with a decreased risk of total BC.SULT1A1(P=0.0011)and CX3CL1(P=0.0005)were associated with an increased risk of ER+BC,whereas beta-NGF(P=0.0001)was associated with an increased risk of ER-BC.Supplem-entary analysis methods validated that the findings were consistent in direction and magnitude.The results of the sensitivity analysis showed that the data were reliable and unbiased.Conclusion Using the MR method,this study confirms that SULT1A1 is a risk factor for overall breast cancer,whereas IL-5 is a protective factor for overall breast cancer.SULT1A1 and CX3CL1 are risk factors for estrogen receptor-positive breast cancer,and beta-NGF is a risk factor for estrogen receptor-negative breast cancer.

关 键 词：乳腺癌 雌激素受体 孟德尔随机化 循环炎症蛋白 

分 类 号：R737.9[医药卫生—肿瘤]