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

作者信息

Luo Li, Gansevoort Ron T, Kieneker Lyanne M, de Boer Rudolf A, Chen Zekai, Aboumsallem Joseph Pierre, Snieder Harold, Thio Chris H L

机构信息

Department of Nephrology, University Medical Center Groningen, University of Groningen, The Netherlands.

Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, The Netherlands.

出版信息

Kidney Med. 2025 Jul 7;7(9):101065. doi: 10.1016/j.xkme.2025.101065. eCollection 2025 Sep.


DOI:10.1016/j.xkme.2025.101065
PMID:40893915
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12396428/
Abstract

RATIONALE & OBJECTIVE: Chronic kidney disease (CKD) is reported to be associated with cancer, especially for urinary tract and lung cancer. However, whether this suggests causality has not been resolved. This study aimed to investigate the causal relation of CKD to overall, urinary tract, and lung cancer. STUDY DESIGN: Mendelian randomization (MR) analysis. SETTING & PARTICIPANTS: Single-nucleotide polymorphism (SNP)-CKD data were obtained from genome-wide association studies of a meta-analysis of CKDGen and UK Biobank. SNP-cancer data from genome-wide association studies of several community-based and cancer-specific consortia were extracted and then meta-analyzed. EXPOSURES: Impaired kidney function (creatinine-based estimated glomerular filtration rate [eGFRcr] <60 mL/min/1.73 m), increased albuminuria (urinary albumin-creatinine ratio [UACR] >30 mg/g), and on a continuous scale, eGFRcr, cystatin C-based eGFR (eGFRcys), and UACR. OUTCOMES: Incidences of overall cancer, urinary tract cancer, and lung cancer. ANALYTICAL APPROACH: Pooled MR estimates of single-SNP Wald ratios were obtained using an inverse variance-weighted method. RESULTS: In inverse variance-weighted MR analyses, a higher genetic liability to impaired kidney function was not significantly associated with higher overall cancer risk (OR, 1.00; 95% CI, 1.00-1.01;  = 0.06). No associations of other kidney phenotypes including increased albuminuria, eGFRcr, eGFRcys, and UACR with overall cancer risk were found at the Bonferroni-corrected significance level (all  > 0.0025). Similarly, risk estimates of generally null were detected in the associations of all these CKD phenotypes with specifically urinary tract and lung cancer (all  > 0.0025). The results of our sensitivity analyses, including pleiotropy-robust MR, reverse MR, and multivariable MR analyses, corroborated the results of our main analyses. LIMITATIONS: Uncertain extrapolation to other ethnicities. CONCLUSIONS: Genetically predicted CKD is not associated with the risk of incident overall, urinary tract, and lung cancer. Our findings thus provide no genetic evidence for a causal relationship between CKD and cancer.

摘要
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9271/12396428/190f5a45e231/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9271/12396428/50024535ec2e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9271/12396428/0a8a1456830a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9271/12396428/190f5a45e231/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9271/12396428/50024535ec2e/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9271/12396428/0a8a1456830a/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9271/12396428/190f5a45e231/gr3.jpg

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本文引用的文献

[1]
Multivariable MR Can Mitigate Bias in Two-Sample MR Using Covariable-Adjusted Summary Associations.

Genet Epidemiol. 2025-1

[2]
Mediators of the association between albuminuria and incident cancer: the PREVEND study.

Clin Kidney J. 2023-12-9

[3]
Albuminuria and the risk of cancer: the Stockholm CREAtinine Measurements (SCREAM) project.

Clin Kidney J. 2023-6-23

[4]
Challenges in undertaking nonlinear Mendelian randomization.

Obesity (Silver Spring). 2023-12

[5]
Mendelian randomization.

Nat Rev Methods Primers. 2022-2-10

[6]
FinnGen provides genetic insights from a well-phenotyped isolated population.

Nature. 2023-1

[7]
Association of chronic kidney disease with total and site-specific cancer incidence in participants of the Japan Public Health Center-based Prospective Study.

Nephrol Dial Transplant. 2023-5-31

[8]
Impairment of kidney function and kidney cancer: A bidirectional Mendelian randomization study.

Cancer Med. 2023-2

[9]
Epidemiology of chronic kidney disease: an update 2022.

Kidney Int Suppl (2011). 2022-4

[10]
Cancer Risk and Mortality in Patients With Kidney Disease: A Population-Based Cohort Study.

Am J Kidney Dis. 2022-10

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