Associations of Genetically Predicted CKD With Urinary Tract Cancer and Lung Cancer: A Mendelian Randomization...

Area of Science:

• Nephrology
• Oncology
• Genetic Epidemiology

Background:

• Chronic kidney disease (CKD) is epidemiologically linked to increased cancer risk, particularly for urinary tract and lung cancers.
• The causal nature of this association remains unresolved, necessitating robust investigation.
• Genetic epidemiology offers a powerful approach to infer causality by leveraging genetic variants as instrumental variables.

Purpose of the Study:

• To investigate the potential causal relationship between chronic kidney disease (CKD) and the risk of developing overall, urinary tract, and lung cancer.
• To utilize Mendelian randomization (MR) analysis to assess causality, overcoming limitations of observational studies.
• To differentiate between association and causation in the CKD-cancer relationship.

Main Methods:

• Mendelian randomization (MR) analysis was employed using single-nucleotide polymorphism (SNP) data.
• Genome-wide association study (GWAS) data for CKD (CKDGen, UK Biobank) and cancer (various consortia) were meta-analyzed.
• Inverse variance-weighted (IVW) methods were used for pooled MR estimates, with sensitivity analyses including pleiotropy-robust, reverse, and multivariable MR.

Main Results:

• A higher genetic liability to impaired kidney function was not significantly associated with an increased risk of overall cancer (OR, 1.00; 95% CI, 1.00-1.01; P=0.06).
• No significant associations were found between various CKD phenotypes (e.g., albuminuria, eGFRcr, eGFRcys) and overall cancer risk at the Bonferroni-corrected significance level.
• Similarly, null risk estimates were observed for the associations between CKD phenotypes and specific risks of urinary tract and lung cancer, corroborated by sensitivity analyses.

Conclusions:

• Genetically predicted chronic kidney disease (CKD) does not appear to causally increase the risk of incident overall, urinary tract, or lung cancer.
• The findings provide no genetic evidence to support a causal link between CKD and cancer development.
• Further research may be needed to explore potential confounding factors or specific subpopulations, considering limitations in extrapolating to diverse ethnicities.