AUTHOR=Chen Weiming , Chen Maohui , Huang Jin , Xie Qichang , Huang Yizhou , Chen Chun , Zhu Yong 

TITLE=Relationships of omega-3 and omega-6 polyunsaturated fatty acids with esophageal diseases: a two-sample Mendelian randomization analysis

JOURNAL=Frontiers in Nutrition

VOLUME=11

YEAR=2024

URL=https://www.frontiersin.org/journals/nutrition/articles/10.3389/fnut.2024.1408647

DOI=10.3389/fnut.2024.1408647

ISSN=2296-861X

ABSTRACT=<sec><title>Introduction</title><p>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.</p></sec><sec><title>Methods</title><p>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 (<ext-link xlink:href="https://gwas.mrcieu.ac.uk/" ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink">https://gwas.mrcieu.ac.uk/</ext-link>) and the GWAS Catalog database (<ext-link xlink:href="https://www.ebi.ac.uk/" ext-link-type="uri" xmlns:xlink="http://www.w3.org/1999/xlink">https://www.ebi.ac.uk/</ext-link>). 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.</p></sec><sec><title>Results</title><p>We found that the circulating omega-3 PUFAs concentration was positively associated with esophageal cancer (<italic>p</italic> = 8 × 10<sup>−4</sup>), and circulating DHA concentration (the main component of omega-3 in food), was also positively associated with esophageal cancer (<italic>p</italic> = 2 × 10<sup>−2</sup>), but no significant association was found between circulating omega-6 PUFAs and esophageal cancer (<italic>p</italic> = 0.17), and circulating LA concentration (the main component of omega-6 in food), was also no significant associated with esophageal cancer (<italic>p</italic> = 0.32). We found no significant relationships of circulating omega-3 and omega-6 PUFAs concentration with four other esophageal diseases.</p></sec><sec><title>Conclusion</title><p>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.</p></sec>