Journal
CLINICAL BREAST CANCER
Volume 23, Issue 4, Pages E182-E188Publisher
CIG MEDIA GROUP, LP
DOI: 10.1016/j.clbc.2023.01.015
Keywords
Genome-wide association study; sIL-6R; IL-6; Mendelian randomization; Genetic variants; Breast cancer
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It is still unclear whether IL-6 is causally associated with the risk of breast cancer. Our two-sample Mendelian randomization (MR) study demonstrated a causal link between a genetically increase in IL-6-signaling and an increase in breast cancer risk. Thus, IL-6 may be a valuable biological indicator for risk assessment, prevention, and treatment of patients with breast cancer.
It is still unclear whether IL-6 is causally associated with the risk of breast cancer. Our two-sample Mendelian randomization (MR) study demonstrated a causal link between a genetically increase in IL-6-signaling and an increase in breast cancer risk. Thus, IL-6 may be a valuable biological indicator for risk assessment, prevention, and treatment of patients with breast cancer. Background: 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. Material and Methods: 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. Results: 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). Conclusion: 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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