From fat to tumor: Exploring the inflammatory bridge via CRP in obesity-related bladder cancer

This study aims to investigate whether C-reactive protein (CRP) mediates the causal relationship between body mass index (BMI) and bladder cancer (BC). Furthermore, the mechanisms and intermediaries involved will be explored, and the proportion of CRP role in this mechanism will be calculated. Two-sample Mendelian randomization (MR), Bayesian weighted MR, and multivariable MR studies were conducted to explore if CRP mediates the causal relationship between BMI and BC, and to quantify the proportion of mediation. Using genetic data, this study provides evidence that elevated levels of CRP may mediate the effect of BMI on the risk of BC. Clinicians should pay closer attention to inflammatory markers such as CRP in obese patients to better prevent BC. But for now that conclusion may be limited to European populations. There is a positive causal relationship between BMI and BC (odds ratio [OR] = 1.655, 95% confidence interval [CI] = 1.122-2.441, P = .011). A positive causal relationship was also found between BMI and CRP (OR = 1.237, 95% CI = 1.175-1.304, P = 9.417 × 10-16). Additionally, CRP was positively associated with BC (OR = 1.401, 95% CI = 1.017-1.929, P = .038). After adjusting for CRP, the causal relationship between BMI and BC was no longer significant (OR = 1.413, 95% CI = 0.959-2.081, P = .079). However, CRP maintained a causal relationship with BC after adjusting for BMI (OR = 1.434, 95% CI = 1.042-1.973, P = .026). The mediation effect of CRP was calculated to be 15.9%. Bayesian weighted MR also showed strong correlations.