Hans Oh, Mingyang Song, Jae Il Shin, Ai Koyanagi, Louis Jacob, Andreas Kronbichler, Gaeun Kim, Michael Eisenhut, Eun Kyoung Choi, Sun Jae Jung, Lin Yang, Marco Solmi, Gwang Hun Jeong, Eunyoung Jung, Brendon Stubbs, Keum Hwa Lee, Eunyoung Cho, Joaquim Radua, Edward Giovannucci, NaNa Keum, Hyo Jin Seong, Nicola Veronese, Hyunbong Park, Lee Smith, Gabriele Gamerith, Giuseppe Grosso, Trevor Thompson, Elena Dragioti, Sarah E Jackson, Leandro Fórnias Machado de Rezende, Shuji Ogino, Jong Yeob Kim, Hans van Vliet, Sung Hwi Hong, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), South London and Maudsley NHS Foundation Trust National Institute for Health Research, NIHR NIHR Collaboration for Leadership in Applied Health Research and Care South London National Institutes of Health, NIH: R35 CA197735 Maudsley Charity King’s College London National Institutes of Health, NIH: R35 CA197735, KHL, HJS, GK, GHJ, and JYK contributed equally to this work. The authors report no funding received for this study. Author Disclosures: The authors report no conflicts of interest. BS is supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR), is in part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and is also supported by the Maudsley Charity, King’s College London, and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding. The time effort of SO was in part supported by US National Institutes of Health grant R35 CA197735. This paper presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the acknowledged institutions. Address correspondence to JIS (e-mail: shinji@yuhs.ac) or EKC (e-mail: ekchoi@yuhs.ac). Supplemental Table 1 is available from the 'Supplementary data'link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/advances. Abbreviation used: ALA, α-linolenic acid, AMSTAR2, A Measurement Tool to Assess Systematic Reviews 2, CUP, Continuous Update Project, DPA, docosapentaenoic acid, GRADE, Grading of Recommendations Assessment, Development and Evaluation, HCC, hepatocellular carcinoma, NA, not assessable, PI, prediction interval, PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, WCRF/AICR, Word Cancer Research Fund/American Institute for Cancer Research., The time effort of SO was in part supported by US National Institutes of Health grant R35 CA197735., Lee, K.H., Seong, H.J., Kim, G., Jeong, G.H., Kim, J.Y., Park, H., Jung, E., Kronbichler, A., Eisenhut, M., Stubbs, B., Solmi, M., Koyanagi, A., Hong, S.H., Dragioti, E., De Rezende, L.F.M., Jacob, L., Keum, N., Van Der Vliet, H.J., Cho, E., Veronese, N., Grosso, G., Ogino, S., Song, M., Radua, J., Jung, S.J., Thompson, T., Jackson, S.E., Smith, L., Yang, L., Oh, H., Choi, E.K., Shin, J.I., Giovannucci, E.L., and Gamerith, G.
Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or ω-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between ω-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta-analyses by study design, we found weak associations between ω-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although ω-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between ω-3 fatty acid consumption and cancer risks. Copyright © 2020 The Author(s) on behalf of the American Society for Nutrition.