Li Bing-Hui, Yan Si-Yu, Li Xu-Hui, Huang Qiao, Luo Li-Sha, Wang Yun-Yun, Huang Jiao, Jin Ying-Hui, Wang Yong-Bo
Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China.
Front Nutr. 2022 Aug 22;9:898279. doi: 10.3389/fnut.2022.898279. eCollection 2022.
The association between coffee and caffeine consumption and the risk of renal cell carcinoma was inconsistent among observational studies, and whether these observed associations were causal remained unclear. Therefore, we performed two-sample Mendelian randomization (MR) study to assess the causal nature of the association.
In this study, 12 and two independent single nucleotide polymorphisms (SNPs) related to coffee and caffeine consumption at a genome-wide significance level of < 5 × 10 were used as instrumental variables (IVs), respectively. Summary-level data for renal cell carcinoma were taken from the FinnGen consortium with up to 174,977 individuals, and the International Agency for Research on Cancer (IARC) with 13,230 individuals. We used inverse-variance weighted (IVW) as the main method, followed by the weighted median method, the MR-Egger regression method, and the MR robust adjusted profile score method. Outlier and pleiotropic variants were assessed by the MR Pleiotropy RESidual Sum and Outlier test and MR-Egger regression. We used meta-analysis methods in fixed-effects to combine the estimates from the two sources.
The genetically predicted coffee consumption was not associated with the risk of renal cell carcinoma in the FinnGen consortium, and the relationship was consistent in the IARC consortium. The pooled odds ratio () per 50% increase of coffee consumption was 0.752 [95% confidence interval (), 0.512-1.105; = 0.147]. In addition, complementary analyses that separated the coffee-related SNPs according to their relationship with blood levels of caffeine metabolites (higher, lower, or unrelated) found no relationship with renal cell carcinoma. The results were consistent after excluding eight SNPs due to potential risk factors at genome-wide significance ( < 5 × 10). Moreover, genetically predicted per 80-mg increase in caffeine consumption was not associated with the risk of renal cell carcinoma (pooled = 0.872, 95% : 0.676-1.125, = 0.292).
Our MR study provided no convincing evidence for a causal effect between coffee and caffeine consumption and the risk of renal cell carcinoma. The associations for renal cell carcinoma need to be verified in well-powered studies.
在观察性研究中，咖啡和咖啡因摄入量与肾细胞癌风险之间的关联并不一致，而且这些观察到的关联是否具有因果关系仍不明确。因此，我们进行了一项两样本孟德尔随机化（MR）研究，以评估这种关联的因果性质。
在本研究中，分别使用12个和2个在全基因组显著性水平（<5×10）下与咖啡和咖啡因摄入量相关的独立单核苷酸多态性（SNP）作为工具变量（IV）。肾细胞癌的汇总数据来自芬兰基因联盟（FinnGen consortium）的多达174,977名个体，以及国际癌症研究机构（IARC）的13,230名个体。我们以逆方差加权（IVW）作为主要方法，随后采用加权中位数法、MR-Egger回归法和MR稳健调整轮廓得分法。通过MR多效性残差和离群值检验以及MR-Egger回归评估离群值和多效性变异。我们使用固定效应的荟萃分析方法来合并来自两个来源的估计值。
在芬兰基因联盟中，基因预测的咖啡摄入量与肾细胞癌风险无关，并且在国际癌症研究机构联盟中这种关系也是一致的。咖啡摄入量每增加50%的合并比值比（OR）为0.752 [95%置信区间（CI），0.512 - 1.105；P = 0.147]。此外，根据与咖啡因代谢物血液水平的关系（较高、较低或无关）对与咖啡相关的SNP进行分离的补充分析发现，与肾细胞癌没有关系。在排除由于全基因组显著性（<5×10）的潜在风险因素导致的8个SNP后，结果仍然一致。此外，基因预测的咖啡因摄入量每增加80毫克与肾细胞癌风险无关（合并OR = 0.872，95% CI：0.676 - 1.125，P = 0.292）。
我们的MR研究没有提供令人信服的证据表明咖啡和咖啡因摄入量与肾细胞癌风险之间存在因果关系。肾细胞癌的这些关联需要在有足够效力的研究中进行验证。
