Role of Reactive C protein in Mediating the Effect of body mass index on bladder cancer Diseases

Abstract

Purpose: To investigate whether C-reactive protein (CRP) can mediate the causal relationship between body mass index (BMI) and the development of bladder cancer (BC), further elucidate the underlying mechanisms and the mediating role of CRP, and quantify the proportion of CRP in this mechanism. Methods: Using two-sample Mendelian randomization and multivariable Mendelian randomization studies, we explored whether CRP serves as a mediator in the causal relationship between BMI and BC, and calculated the proportion of mediation in this context. Results: There is a positive causal relationship between BMI and BC (OR=1.655, 95% CI=1.122-2.441, p=0.011). BMI is positively causally related to CRP (OR=1.237, 95% CI=1.175-1.304, p=9.417×10-16). CRP is also positively causally related to BC (OR=1.401, 95% CI=1.017-1.929, p=0.038). After adjusting for CRP, there is no causal relationship between BMI and BC (OR=1.413, 95% CI=0.959-2.081, p=0.079). Even after controlling for BMI, there is still a causal relationship between CRP and BC (OR=1.434, 95% CI=1.042-1.973, p=0.026). The mediating effect of CRP is 15.9%. Conclusion: Using genetic data, this study provides evidence that higher levels of C-reactive protein (CRP) may serve as a mediator in the pathway through which BMI leads to BC. Clinical practitioners should pay closer attention to the inflammatory marker CRP levels in obese individuals for better BC prevention strategies.