Causal Association between Chronic Kidney Disease and Risk of 19 Site-Specific Cancers: A Mendelian Randomization Study

Abstract Background: Results of previous observational studies examining the risk of cancer among patients with chronic kidney disease (CKD) are conflicting. We here explore the causal relationship between estimated glomerular filtration rate (eGFR) and albuminuria, two principal measurements of CKD, and 19 site-specific cancers using Mendelian randomization (MR) analysis. Methods: Single-nucleotide polymorphisms reported to be strongly correlated with eGFR and albuminuria in recent large genome-wide association studies were used as instrumental variables to investigate the causal relationship with cancer using summary-level statistics from several cancer-specific consortia, as well as data of 347,408 participants in the UK Biobank and 260,405 participants in the FinnGen. Results: Our data showed that impaired kidney function was associated with higher odds of leukemia [OR = 1.23; 95% confidence interval (CI), 1.06–1.43; P = 0.007], cervical cancer (OR = 1.22; 95% CI, 1.04–1.43; P = 0.017), and female renal cell carcinoma (OR = 1.4; 95% CI, 1.12–1.77; P = 0.004), per 10% decrease in eGFR. The ORs were 1.21 (95% CI, 1.07–1.36; P = 0.002) for colorectal cancer and 0.76 (95% CI, 0.62–0.92; P = 0.006) for non–Hodgkin lymphoma, per doubling odds of albuminuria. In multivariable MR, effect sizes of eGFR–cervical cancer remained strong after adjusting for confounders. Conclusions: The current study indicates that progression of CKD contributes to carcinogenesis of renal cell carcinoma, leukemia, cervical, and colorectal cancer. Impact: The potential association of kidney function and albuminuria with certain cancers warrants further investigation in order to provide appropriate recommendations regarding cancer screening among patients with CKD.