简介：观察性研究发现吸烟和饮酒与患肾细胞癌的可能性之间存在相关性。然而，这些关联是否表明因果关系尚不清楚。方法：为了确定这些联系是否表明因果关系，我们使用两个样本方法进行了孟德尔随机化 (MR) 分析。对于每日吸烟数量、终生吸烟指数、开始吸烟和每周饮酒，我们采用 44、108、174 和 76 个单核苷酸多态性 (SNP) 作为工具变量。结果数据来自 FinnGen Alliance，该联盟总共包括 429,290 人。使用逆方差加权（IVW）方法进行MR分析来估计因果效应。为了解决由于方向多效性而可能违反 MR 假设的问题，我们进行了 MR-Egger 回归和 MR-PRESSO（孟德尔随机多效性残差和离群值）分析。结果：受遗传影响的吸烟开始与患肾细胞癌的风险直接相关（OR = 1.55，95% CI：1.04-2.33；p = 0.03）。每日吸烟量和终生吸烟指数与肾细胞癌风险之间没有发现因果关系。每周饮酒的遗传倾向显示肾细胞癌的风险降低（OR = 0.45，95% CI：0.26-0.81；p = 0.007）。讨论：我们的研究表明饮酒与降低肾细胞癌风险之间存在潜在因果关系，而与吸烟没有观察到这种关联。需要进一步的研究来证实这些发现。版权所有 © 2024 Cui、Du、Xue、Zhao 和 Li。

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.Copyright © 2024 Cui, Du, Xue, Zhao and Li.