Keum Hwa Lee ¹, Hyo Jin Seong ², Gaeun Kim ³, Gwang Hun Jeong ⁴, Jong Yeob Kim ², Hyunbong Park ⁵, Eunyoung Jung ⁵, Andreas Kronbichler ⁶, Michael Eisenhut ⁷, Brendon Stubbs ^8,9,10, Marco Solmi ¹¹, Ai Koyanagi ^12,13, Sung Hwi Hong ^2,14, Elena Dragioti ¹⁵, Leandro Fórnias Machado de Rezende ¹⁶, Louis Jacob ^12,17, NaNa Keum ^18,19, Hans J van der Vliet ²⁰, Eunyoung Cho ^21,22, Nicola Veronese ²³, Giuseppe Grosso ²⁴, Shuji Ogino ^{25, 26,27,28}, Mingyang Song ^18,26,29,30, Joaquim Radua ^31,32,33,34, Sun Jae Jung ^26,35, Trevor Thompson ³⁶, Sarah E Jackson ³⁷, Lee Smith ³⁸, Lin Yang ^39,40, Hans Oh ⁴¹, Eun Kyoung Choi ^42,*, Jae Il Shin ^1,*, Edward L Giovannucci ^18,22, Gabriele Gamerith ⁴³

¹Department of Pediatrics, Yonsei University College of Medicine, Seoul, Republic of Korea.
²Yonsei University College of Medicine, Seoul, Republic of Korea.
³Keimyung University College of Nursing, Daegu, Republic of Korea.
⁴College of Medicine, Gyeongsang National University, Jinju, Republic of Korea.
⁵Yonsei University Graduate School, Department of Nursing, Seoul, Republic of Korea.
⁶Department of Internal Medicine IV (Nephrology and Hypertension), Medical University Innsbruck, Innsbruck, Austria.
⁷Department of Pediatrics, Luton & Dunstable University Hospital NHS Foundation Trust, Luton, United Kingdom.
⁸Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
⁹South London and Maudsley NHS Foundation Trust, London, United Kingdom.
¹⁰Faculty of Health, Social Care and Education, Anglia Ruskin University, Chelmsford, United Kingdom.
¹¹Department of Neuroscience, University of Padova, Padova, Italy.
¹²Parc Sanitari Sant Joan de Déu/CIBERSAM, Universitat de Barcelona, Fundació Sant Joan de Déu, Sant Boi de Llobregat, Barcelona, Spain.
¹³ICREA, Barcelona, Spain.
¹⁴Department of Global Health and Population, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁵Pain and Rehabilitation Centre, Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.
¹⁶Universidade Federal de São Paulo, Escola Paulista de Medicina, Departamento de Medicina Preventiva, São Paulo, São Paulo, Brazil.
¹⁷Faculty of Medicine, University of Versailles Saint-Quentin-en-Yvelines, Montigny-le-Bretonneux, France.
¹⁸Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
¹⁹Department of Food Science and Biotechnology, Dongguk University, Goyang, Republic of Korea.
²⁰Department of Medical Oncology, Amsterdam UMC, Cancer Center Amsterdam, VU University, Amsterdam, The Netherlands.
²¹Department of Dermatology, The Warren Alpert Medical School, Brown University, Providence, RI, USA.
²²Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²³National Research Council, Neuroscience Institute, Aging Branch, Padova, Italy.
²⁴Department of Biomedical and Biotechnological Sciences, University of Catania, Catania, Italy.
²⁵Cancer Immunology and Cancer Epidemiology Programs, Dana-Farber Harvard Cancer Center, Boston, MA, USA.
²⁶Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA.
²⁷Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
²⁸Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, MA, USA.
²⁹Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³⁰Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
³¹Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
³²Mental Health Research Networking Center (CIBERSAM), Barcelona, Spain.
³³Department of Psychosis Studies, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom.
³⁴Centre for Psychiatric Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
³⁵Department of Preventive Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea.
³⁶Department of Psychology, University of Greenwich, London, United Kingdom.
³⁷Department of Behavioral Science and Health, University College London, London, United Kingdom.
³⁸The Cambridge Centre for Sport and Exercise Sciences, Anglia Ruskin University, Chelmsford, United Kingdom.
³⁹Department of Cancer Epidemiology and Cancer Prevention, Alberta Health Services, Calgary, Canada.
⁴⁰Departments of Oncology and Community Health Sciences, Cumming School of Medicine, University of Calgary, Calgary, Canada.
⁴¹School of Social Work, University of Southern California, CA, USA.
⁴²Mo-Im Kim Nursing Research Institute, Yonsei University College of Nursing, Seoul, Republic of Korea.
⁴³Internal Medicine V, Department of Hematology and Oncology, Medical University Innsbruck, Innsbruck, Austria.

^*Corresponding author

Abstract
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.