The causal relationship between osteoarthritis and bladder cancer: A Mendelian randomization study

Cancer Med. 2023 Dec 15;13(1):e6829. doi: 10.1002/cam4.6829. Online ahead of print.

Abstract

Objective: The causal association between osteoarthritis (OA) and bladder cancer remains unclear. This Mendelian randomization (MR) study was carried out to assess the potential causal effects of any OA, knee OA and hip OA, and bladder cancer.

Method: Genome-wide association study (GWAS) summary data for OA and bladder cancer were obtained in GWAS CATALOG, UK Biobank, and FinnGen Consortium. Inverse-variance weighted (IVW) approach was primarily conducted to evaluate the causal relationships between OA and bladder cancer, and MR-Egger intercept and Cochran's Q test were mainly used to estimate heterogeneity and pleiotropy. MR-PRESSO was used to test the presence of horizontal outliers. Leave-one-out analysis was utilized to ensure the reliability of the results.

Results: A higher genetic predisposition to any OA has a causal association with bladder cancer risk, while neither knee OA nor hip OA is causally linked to bladder cancer. MR-Egger intercept analysis exhibited that any OA and knee OA had no pleiotropic effect on the risk of bladder cancer, and Cochran's Q test showed that any OA, knee OA and hip OA had no heterogeneity on bladder cancer risk. Neither MR PRESSO analysis nor leave-one-out analysis revealed any outlier SNPs.

Conclusions: This MR study exhibited a positive cause-and-effect relationship between any type of OA and bladder cancer risk, but not between site-specific OA, knee OA and hip OA, and bladder cancer. Attention should be paid to the screening and prevention of bladder cancer in OA patients at any site.

Keywords: Mendelian randomization; any osteoarthritis; bladder cancer; hip osteoarthritis; knee osteoarthritis.