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Updated: Jul 14, 2025
Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Therapeutic potential of single-nucleotide polymorphism-mediated interleukin-6 receptor blockade in cancer treatment:
Shuwan Zhang1,2, Wenchuan Zhang1,3, Hanxue Sun1
1Department of Pathology, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning Province, China.
Background:
Interleukin-6 (IL-6) is a crucial member of the cytokine network and plays a pivotal role in the pathogenesis of various diseases, including cancer. IL-6 receptor (IL-6R) blockade is widely employed as a therapeutic strategy; however, its efficacy in anticancer therapy remains ambiguous.
Methods:
An inverse variance-weighted Mendelian randomization (MR) analysis was conducted to assess the causal effects exerted by IL-6R blockade in remediating cancer. Drug-targeted single-nucleotide polymorphisms (SNPs) were introduced within 300 kb of the IL-6R gene. An instrumental variable comprising 26 SNPs represented IL-6 signaling downregulation and C-reactive protein level reduction. Datasets pertaining to the 33 types of cancer investigated in this study were acquired from the FinnGen genome-wide association study.
Results:
The selected instrumental variable lowered fibrinogen levels, confirming its ability to mimic IL-6R blockade. IL-6R blockade exhibited therapeutic effects on five different cancer types documented in the FinnGen database (N = 334,364, including 76,781 cancer patients): bladder (odds ratios (OR) = 0.563), laryngeal (OR = 0.293), eye (OR = 0.098), gallbladder (OR = 0.059), and myeloid leukemia (OR = 0.442); however, it simultaneously elevated the risk of developing basal cell carcinoma (OR = 1.312) and melanoma (OR = 1.311). Sensitivity analyses did not alter the primary results.
Conclusion:
Therefore, this study aimed to evaluate the potential and efficacy of SNP-based IL-6R blockade in treating cancer.
Insights
Interleukin-6 receptor (IL-6R) blockade shows promise in treating several cancers, but increases risk for others. This Mendelian randomization study evaluated IL-6R blockade
Area of Science:
- Oncology
- Immunology
- Genetics
Background:
- Interleukin-6 (IL-6) is a key cytokine implicated in cancer development.
- Blocking the IL-6 receptor (IL-6R) is a therapeutic strategy, but its anticancer efficacy is unclear.
Purpose of the Study:
- To assess the causal impact of IL-6R blockade on various cancer types using a Mendelian randomization approach.
- To evaluate the potential and efficacy of single-nucleotide polymorphism (SNP)-based IL-6R blockade in cancer treatment.
Main Methods:
- An inverse variance-weighted Mendelian randomization (MR) analysis was performed.
- Drug-targeted SNPs within 300 kb of the IL-6R gene were used as instrumental variables.
- Data from the FinnGen genome-wide association study, encompassing 33 cancer types, were analyzed.
Main Results:
- IL-6R blockade demonstrated therapeutic effects in bladder, laryngeal, eye, gallbladder, and myeloid leukemia.
- Conversely, IL-6R blockade was associated with an increased risk of basal cell carcinoma and melanoma.
- Sensitivity analyses confirmed the primary findings, with no significant alterations.
Conclusions:
- SNP-based IL-6R blockade shows a dual effect, offering therapeutic benefits for some cancers while elevating risk for others.
- Further research is warranted to refine IL-6R blockade strategies for optimal cancer treatment.
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