Abstract
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.
Keywords
Abbreviations:
sIL-6R (soluble IL-6 receptor), GWAS (Genome-wide association study), MR (Mendelian randomization), SNP (Single nucleotide polymorphism), IVW (Inverse variance weighted)To read this article in full you will need to make a payment
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Article info
Publication history
Published online: February 04, 2023
Accepted:
January 31,
2023
Received in revised form:
January 31,
2023
Received:
February 22,
2022
Publication stage
In Press Journal Pre-ProofIdentification
Copyright
© 2023 Elsevier Inc. All rights reserved.
