Causal association between chronic kidney disease and risk of 19 site-specific cancers: A Mendelian randomization study
Menée à l'aide d'une méthode de randomisation mendélienne et de données des bases "UK Biobank" et "FinnGen" portant sur 607 813 patients atteints d'insuffisance rénale chronique, cette étude analyse le risque de cancer (19 localisations) lié à cette insuffisance
Background: Results of previous observational studies examining the risk of cancer among chronic kidney disease (CKD) patients 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 (odds ratio [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 odds ratios 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.