Chen Weiming, Chen Maohui, Huang Jin, Xie Qichang, Huang Yizhou, Chen Chun, Zhu Yong
Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
Key Laboratory of Cardio-Thoracic Surgery (Fujian Medical University), Fujian Province University, Fuzhou, China.
Front Nutr. 2024 Jul 17;11:1408647. doi: 10.3389/fnut.2024.1408647. eCollection 2024.
Omega-3 polyunsaturated fatty acids (PUFAs) have been widely studied and used as nutritional supplements because of their anti-inflammatory effects. Previous studies have shown an association between polyunsaturated fatty acids such as omega-3 and omega-6 PUFAs with the development of malignant tumors. However, the relationships of omega-3 and omega-6 PUFAs with esophageal diseases have not been characterized.
Mendelian randomization (MR) is a statistical method for identifying instrumental variables (IVs) from genome-wide association study (GWAS) data, and is associated with little confounding by environmental or other disease-related factors. We used genome-wide association study (GWAS) data from previously published studies on circulating concentrations of omega-3, omega-6, docosahexaenoic acid (DHA) and linoleic acid (LA), as well as esophageal cancer and other esophageal diseases, which were downloaded from the IEU OpenGwas database (https://gwas.mrcieu.ac.uk/) and the GWAS Catalog database (https://www.ebi.ac.uk/). The inverse variance-weighted approach was used as the principal analysis, and the MR-Egger and weighted median methods were used alongside. A series of sensitivity analyses were used to ensure the robustness of the causality estimates.
We found that the circulating omega-3 PUFAs concentration was positively associated with esophageal cancer ( = 8 × 10), and circulating DHA concentration (the main component of omega-3 in food), was also positively associated with esophageal cancer ( = 2 × 10), but no significant association was found between circulating omega-6 PUFAs and esophageal cancer ( = 0.17), and circulating LA concentration (the main component of omega-6 in food), was also no significant associated with esophageal cancer ( = 0.32). We found no significant relationships of circulating omega-3 and omega-6 PUFAs concentration with four other esophageal diseases.
This study indicates that higher levels of circulating omega-3 PUFAs and DHA concentrations may be a risk factor for the development of esophageal cancer. Conversely, an increased omega-6/omega-3 ratio may serve as a protective factor against esophageal cancer. These findings have significant implications for the clinical application of omega-3 PUFAs and the prevention and treatment of esophageal cancer.
ω-3多不饱和脂肪酸（PUFAs）因其抗炎作用而被广泛研究并用作营养补充剂。先前的研究表明，ω-3和ω-6多不饱和脂肪酸等多不饱和脂肪酸与恶性肿瘤的发生有关。然而，ω-3和ω-6多不饱和脂肪酸与食管疾病的关系尚未明确。
孟德尔随机化（MR）是一种从全基因组关联研究（GWAS）数据中识别工具变量（IVs）的统计方法，且受环境或其他疾病相关因素的混杂影响较小。我们使用了先前发表的关于ω-3、ω-6、二十二碳六烯酸（DHA）和亚油酸（LA）循环浓度以及食管癌和其他食管疾病的全基因组关联研究（GWAS）数据，这些数据从IEU OpenGwas数据库（https://gwas.mrcieu.ac.uk/）和GWAS Catalog数据库（https://www.ebi.ac.uk/）下载。采用逆方差加权法作为主要分析方法，并同时使用MR-Egger法和加权中位数法。进行了一系列敏感性分析以确保因果估计的稳健性。
我们发现循环中的ω-3多不饱和脂肪酸浓度与食管癌呈正相关（= 8×10），循环中的DHA浓度（食物中ω-3的主要成分）也与食管癌呈正相关（= 2×10），但循环中的ω-6多不饱和脂肪酸与食管癌之间未发现显著关联（= 0.17），循环中的LA浓度（食物中ω-6的主要成分）与食管癌也无显著关联（= 0.32）。我们发现循环中的ω-3和ω-6多不饱和脂肪酸浓度与其他四种食管疾病无显著关系。
本研究表明，循环中较高水平的ω-3多不饱和脂肪酸和DHA浓度可能是食管癌发生的危险因素。相反，ω-6/ω-3比值升高可能是预防食管癌的保护因素。这些发现对ω-3多不饱和脂肪酸的临床应用以及食管癌的防治具有重要意义。
