The causal relationship between smoking, alcohol consumption, and renal clear cell carcinoma: a Mendelian...

Introduction: Observational studies have found a correlation between the consumption of tobacco and alcohol and the likelihood of developing renal cell carcinoma. However, whether these associations indicate causal relationships is unclear. Methods: To establish if these connections indicate causal relationships, we performed a Mendelian Randomization (MR) analysis using a two-sample approach. For the number of daily cigarettes, lifetime smoking index, smoking initiation, and weekly drinking, we employed 44, 108, 174, and 76 single nucleotide polymorphisms (SNPs) as instrumental variables. Outcome data were obtained from the FinnGen Alliance, which included a combined total of 429,290 individuals. The MR analysis was conducted using the inverse-variance weighted (IVW) method to estimate causal effects. To address potential violations of MR assumptions due to directional pleiotropy, we performed MR-Egger regression and MR-PRESSO (Mendelian Randomization Pleiotropy RESidual Sum and Outlier) analysis. Results: Genetically influenced smoking initiation was directly associated with the risk of developing renal cell carcinoma (OR = 1.55, 95% CI: 1.04-2.33; p = 0.03). No causal relationship was found between daily cigarette consumption and lifetime smoking index with the risk of renal cell cancer. Genetic predisposition for weekly alcohol consumption showed a reduced risk of renal cell cancer (OR = 0.45, 95% CI: 0.26-0.81; p = 0.007). Discussion: Our study suggests a potential causal relationship between alcohol consumption and reduced risk of renal cell cancer, while no such association was observed with smoking. Further research is needed to confirm these findings.