Association of branched-chain amino acids and risk of three urologic cancers: a Mendelian randomization study

Background: Multiple studies suggest a plausible connection between urologic cancers and branched-chain amino acids (BCAAs) breakdown metabolic enzymes. Nevertheless, there is scarce exploration into the variations in circulating BCAAs. In our research, we utilize bidirectional, two-sample Mendelian randomization (MR) analysis to predict the link between BCAAs levels and three distinct types of urological tumors.

Methods: The study examined data from the UK Biobank, including a comprehensive genome-wide association study (GWAS) of total BCAAs, leucine, isoleucine, and valine, alongside three urological system tumors [prostate cancer (PCa), kidney cancer, and bladder cancer] sourced from the Medical Research Council Integrative Epidemiology Unit (MRC-IEU) and FinnGen Consortium databases. The primary analytical approach involved the use of the inverse variance weighted (IVW) method, complemented by MR-PRESSO global testing and MR-Egger regression to identify potential horizontal pleiotropy. Heterogeneity was evaluated using the Cochran Q test.

Results: The levels of circulating total BCAAs [odds ratio (OR) =1.002688, 95% confidence interval (CI): 1.000, 1.005, P=0.03], leucine (OR =1.0038, 95% CI: 1.001, 1.007, P=0.008), isoleucine (OR =1.003352, 95% CI: 1.000, 1.007, P=0.04), and valine (OR =1.00279, 95% CI: 1.001, 1.005, P=0.009) showed positive associations with PCa risk. However, there was inadequate evidence to establish a link between BCAAs and bladder or kidney cancer.

Conclusions: In summary, an association existed between elevated levels of circulating total BCAAs, leucine, isoleucine, and valine, and an increased risk of PCa. However, no correlation was detected between BCAAs and kidney or bladder cancer.