Genetic influence of coffee intake on bladder cancer risk: a two-sample Mendelian randomization analysis

<i>Background</i>. Bladder cancer (BLCA) is one of the most common malignancies of the urinary system, presenting significant public health challenges due to its rising incidence and associated healthcare costs. Despite known risk factors such as genetic predisposition and environmental exposures, the relationship between coffee consumption and the risk of BLCA remains contentious and inadequately understood. <i>Method</i>. This study employed univariable Mendelian randomization (UVMR) to assess the causal relationship between genetically predicted coffee intake and BLCA risk. Genetic variants associated with coffee intake were used as instrumental variables to estimate this potential causal relationship. We also used multivariable Mendelian Randomization (MVMR) to adjust for smoking status to determine the independent impact of coffee on BLCA. Potential mechanisms were explored through two-step MR and bioinformatics analyses. <i>Result</i>. UVMR revealed a significant positive association between genetically driven coffee intake and BLCA risk (OR = 2.074, 95% CI 1.014-4.244, <i>P</i> = 0.046). MVMR showed that there was a significant positive correlation between coffee intake and BLCA (OR = 2.019, 95% CI 1.043-3.910, <i>P</i> = 0.037) after adjustment for smoking. These findings indicate that coffee intake may be an independent risk factor for BLCA. <i>Conclusion</i>. Our study provides genetic evidence supporting a potential association between coffee intake and BLCA risk. While these findings suggest a possible link, moderation in coffee intake may be advisable. Additionally, the study highlights potential mechanisms that warrant further exploration in future research.