Xu Huan, Wang Xuanyang, Xu Xiaoqing, Liu Lin, Zhang Yuntao, Yan Xuemin, Zhang Yingfeng, Dang Keke, Li Ying
Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China; The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, China.
Clin Nutr. 2023 Dec;42(12):2493-2502. doi: 10.1016/j.clnu.2023.10.019. Epub 2023 Oct 23.
Studies have suggested a possible relevance between branched-chain amino acid (BCAA) catabolic enzymes and cancers. However, few studies have explored the variation in circulating concentrations of BCAAs. Our study used bi-directional, two-sample Mendelian randomization (MR) analysis for predicting the causality between the BCAA levels and 9 types of cancers.
The largest genome-wide association studies (GWAS) provided data for total BCAAs, valine, leucine, and isoleucine from the UK Biobank. Data on multiple cancer endpoints were collected from various sources, such as the International Lung Cancer Consortium (ILCCO), the Pancreatic Cancer Cohort Consortium 1 (PanScan1), the Breast Cancer Association Consortium (BCAC), the FinnGen Biobank, and the Ovarian Cancer National Alliance (OCAC). The mainly analysis method was the inverse-variance-weighted (IVW). For assessing horizontal pleiotropy, the researchers performed MR-Egger regression and MR-PRESSO global test. Finally, the Cochran's Q test served for evaluating the heterogeneity.
Circulating total BCAAs levels (OR 1.708, 95%CI 1.168, 2.498; p = 0.006), valine levels (OR 1.747, 95%CI 1.217, 2.402; p < 0.001), leucine levels (OR 1.923, 95%CI 1.279, 2.890; p = 0.002) as well as isoleucine levels (OR 1.898, 95%CI 1.164, 3.094; p = 0.010) positively correlated with the squamous cell lung cancer risk. Nevertheless, no compelling evidence was found to support a causal link between BCAAs and any other examined cancers.
Increased circulating total-BCAAs levels, leucine levels, isoleucine levels and valine levels had higher hazard of squamous cell lung cancer. No such associations were found for BCAAs with other cancers.
研究表明支链氨基酸（BCAA）分解代谢酶与癌症之间可能存在关联。然而，很少有研究探讨循环中BCAAs浓度的变化。我们的研究采用双向两样本孟德尔随机化（MR）分析来预测BCAAs水平与9种癌症之间的因果关系。
最大规模的全基因组关联研究（GWAS）提供了来自英国生物银行的总BCAAs、缬氨酸、亮氨酸和异亮氨酸的数据。多种癌症终点的数据来自不同来源，如国际肺癌联盟（ILCCO）、胰腺癌队列联盟1（PanScan1）、乳腺癌协会联盟（BCAC）、芬兰生物银行和卵巢癌国家联盟（OCAC）。主要分析方法是逆方差加权（IVW）。为评估水平多效性，研究人员进行了MR-Egger回归和MR-PRESSO全局检验。最后， Cochr an's Q检验用于评估异质性。
循环中总BCAAs水平（比值比1.708，95%置信区间1.168，2.498；p = 0.006）、缬氨酸水平（比值比1.747，95%置信区间1.217，2.402；p < 0.001）、亮氨酸水平（比值比1.923，95%置信区间1.279，2.890；p = 0.002）以及异亮氨酸水平（比值比1.898，95%置信区间1.164，3.094；p = 0.010）与肺鳞状细胞癌风险呈正相关。然而，未发现有力证据支持BCAAs与任何其他所研究癌症之间存在因果联系。
循环中总BCAAs水平、亮氨酸水平、异亮氨酸水平和缬氨酸水平升高会增加肺鳞状细胞癌的风险。未发现BCAAs与其他癌症存在此类关联。
