孟德尔随机化
乳腺癌
医学
肿瘤科
全基因组关联研究
优势比
内科学
癌症
置信区间
遗传关联
生物信息学
单核苷酸多态性
基因型
遗传学
生物
基因
遗传变异
作者
Min Zhang,Ning Ma,Renxi Wang
标识
DOI:10.1016/j.clbc.2023.01.015
摘要
Previous studies have shown an important role of interleukin 6 (IL-6) in the progression and metastasis of breast cancer. The present 2-sample Mendelian randomization (MR) study aimed to identify the genetic causal link between IL-6 and breast cancer.IL-6-signaling and its negative regulator soluble IL-6 receptor (sIL-6R) genetic instruments were chosen from 2 large-scale genome-wide association studies (GWAS) of 204,402 and 3,301 European individuals, respectively. GWAS for breast cancer (14,910 cases and 17,588 controls of European ancestry) was used to evaluate the effect of IL-6-signaling- or sIL-6R-associated genetic instrumental variants on breast cancer risk by performing a 2-sample MR study.As IL-6-signaling genetically increased, breast cancer risk increased based on weighted median (odds ratio [OR] = 1.396, 95% confidence interval [CI]: 1.008-1.934, P = .045) and inverse variance weighted (IVW) (OR = 1.370, 95% CI: 1.032-1.819, P = .030). Otherwise, as sIL-6R genetically increased, the risk of breast cancer decreased based on weighted median (OR = 0.975, 95% CI: 0.947-1.004, P = .097) and IVW (OR = 0.977, 95% CI: 0.956-0.997, P = .026).Our analysis suggests a causal link between a genetically-linked increase in IL-6-signaling and increase in the risk of breast cancer. Thus, inhibition of IL-6 may be a valuable biological indicator for risk assessment, prevention, and treatment of patients with breast cancer.
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