Causal relationship between several autoimmune diseases and renal malignancies: A two-sample mendelian randomization...

Area of Science:

• Genetics
• Autoimmunology
• Oncology

Background:

• Observational studies suggest a link between autoimmune diseases (AD) and various cancers.
• Establishing a causal relationship between AD and malignancy has been challenging due to difficulties in determining temporal order.

Purpose of the Study:

• To investigate the genetic causality between systemic autoimmune diseases and renal malignancy using a large-scale genome-wide association study (GWAS) dataset.
• To explore potential bidirectional genetic influences between AD and kidney cancer.

Main Methods:

• Utilized single nucleotide polymorphisms (SNPs) associated with systemic AD as instrumental variables in a Mendelian randomization framework.
• Employed inverse variance weighting (IVW), MR-Egger, and weighted median methods for causal inference.
• Conducted sensitivity analyses to assess heterogeneity, pleiotropy, and instrumental variable validity.

Main Results:

• Positive associations with increased renal malignancy risk were found for acute and subacute iridocyclitis, ankylosing spondylitis, and spondyloarthritis.
• Negative associations with renal malignancy risk were observed for coxarthrosis, juvenile rheumatism, and systemic lupus erythematosus.
• Sensitivity analyses confirmed the robustness of the findings, indicating no significant heterogeneity or pleiotropy.

Conclusions:

• The study provides evidence for a causal relationship between specific systemic autoimmune diseases and renal malignancies.
• Findings highlight the importance of considering AD as a risk factor for kidney cancer and offer genetic insights into renal malignancy development.