Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis

Theodore M Brasky¹, Erinn M Hade², David E Cohn³, Alison M Newton⁴, Stacey Petruzella⁵, Kelli O'Connell⁵, Kimberly A Bertrand⁶, Linda S Cook⁷, Immaculata De Vivo⁸, Mengmeng Du⁵, Jo L Freudenheim⁹, Christine M Friedenreich¹⁰, Marc T Goodman¹¹, Jessica Gorzelitz¹², Torukiri I Ibiebele¹³, Vittorio Krogh¹⁴, Linda M Liao¹⁵, Loren Lipworth¹⁶, Lingeng Lu¹⁷, Susan McCann¹⁸, Tracy A O'Mara¹⁹, Julie R Palmer⁶, Jeanette Ponte⁵, Anna Prizment²⁰, Harvey Risch¹⁷, Sven Sandin²¹, Leo J Schouten²², Veronica Wendy Setiawan²³, Xiao-Ou Shu¹⁶, Britton Trabert²⁴, Piet A van den Brandt²², Penelope M Webb¹³, Nicolas Wentzensen²⁵, Lynne R Wilkens²⁶, Alicja Wolk²⁷, Herbert Yu²⁸, Marian L Neuhouser²⁹

Affiliations

¹ Department of Internal Medicine, Division of Medical Oncology, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address: Theodore.Brasky@osumc.edu.
² Department of Internal Medicine, Division of Medical Oncology, The Ohio State University College of Medicine, Columbus, OH, USA; Department of Population Health, Division of Biostatistics, New York University Grossman School of Medicine, New York, NY, USA.
³ Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Columbus, OH, USA.
⁴ Department of Internal Medicine, Division of Medical Oncology, The Ohio State University College of Medicine, Columbus, OH, USA.
⁵ Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁶ Slone Epidemiology Center at Boston University, Boston University School of Medicine, Boston, MA, USA.
⁷ Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
⁸ Department of Epidemiology, Harvard University, Boston, MA, USA.
⁹ Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
¹⁰ Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, AB, Canada; Departments of Oncology and Community Health Sciences, University of Calgary Cumming School of Medicine, Calgary, AB, Canada.
¹¹ Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
¹² Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
¹³ Population Health Department, QIMR Berghofer Medical Research Institute, Herston, Qld, Australia.
¹⁴ Fondazione IRCCS - Istituto Nazionale dei Tumori di Milan, Milan, Italy.
¹⁵ Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute USA, Bethesda, MD, USA.
¹⁶ Department of Medicine, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁷ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
¹⁸ Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹⁹ Computational Biology and Genetics Department, QIMR Berghofer Medical Research Institute, Herston, Qld, Australia.
²⁰ Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
²¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Seaver Autism Center for Research and Treatment at Mount Sinai, New York, NY, USA.
²² Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
²³ Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
²⁴ Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Utah School of Medicine and Huntsman Cancer Institute, Salt Lake City, UT, USA.
²⁵ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute USA, Rockville, MD, USA.
²⁶ Cancer Center, University of Hawaii, Honolulu, HI, USA.
²⁷ Institute of Environmental Medicine, Unit of Cardiovascular and Nutritional Epidemiology, Karolinska Institute, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
²⁸ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
²⁹ Cancer Prevention Program, Division of Public Health Science, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

PMID: 36934308
PMCID: PMC10025515
DOI: 10.1016/j.ygyno.2022.10.015

Meta-Analysis

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis

Theodore M Brasky et al. Gynecol Oncol. 2023 Feb.

. 2023 Feb:169:137-146.

doi: 10.1016/j.ygyno.2022.10.015. Epub 2022 Oct 28.

Authors

Affiliations

¹ Department of Internal Medicine, Division of Medical Oncology, The Ohio State University College of Medicine, Columbus, OH, USA. Electronic address: Theodore.Brasky@osumc.edu.
² Department of Internal Medicine, Division of Medical Oncology, The Ohio State University College of Medicine, Columbus, OH, USA; Department of Population Health, Division of Biostatistics, New York University Grossman School of Medicine, New York, NY, USA.
³ Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Columbus, OH, USA.
⁴ Department of Internal Medicine, Division of Medical Oncology, The Ohio State University College of Medicine, Columbus, OH, USA.
⁵ Department of Epidemiology & Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁶ Slone Epidemiology Center at Boston University, Boston University School of Medicine, Boston, MA, USA.
⁷ Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA.
⁸ Department of Epidemiology, Harvard University, Boston, MA, USA.
⁹ Department of Epidemiology and Environmental Health, University at Buffalo, Buffalo, NY, USA.
¹⁰ Cancer Epidemiology and Prevention Research, Cancer Care Alberta, Alberta Health Services, Calgary, AB, Canada; Departments of Oncology and Community Health Sciences, University of Calgary Cumming School of Medicine, Calgary, AB, Canada.
¹¹ Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
¹² Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
¹³ Population Health Department, QIMR Berghofer Medical Research Institute, Herston, Qld, Australia.
¹⁴ Fondazione IRCCS - Istituto Nazionale dei Tumori di Milan, Milan, Italy.
¹⁵ Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute USA, Bethesda, MD, USA.
¹⁶ Department of Medicine, Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA.
¹⁷ Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA.
¹⁸ Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, NY, USA.
¹⁹ Computational Biology and Genetics Department, QIMR Berghofer Medical Research Institute, Herston, Qld, Australia.
²⁰ Department of Medicine, Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, MN, USA.
²¹ Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Seaver Autism Center for Research and Treatment at Mount Sinai, New York, NY, USA.
²² Department of Epidemiology, GROW-School for Oncology and Developmental Biology, Maastricht University, Maastricht, The Netherlands.
²³ Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA, USA.
²⁴ Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA; Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University of Utah School of Medicine and Huntsman Cancer Institute, Salt Lake City, UT, USA.
²⁵ Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute USA, Rockville, MD, USA.
²⁶ Cancer Center, University of Hawaii, Honolulu, HI, USA.
²⁷ Institute of Environmental Medicine, Unit of Cardiovascular and Nutritional Epidemiology, Karolinska Institute, Stockholm, Sweden; Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
²⁸ Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
²⁹ Cancer Prevention Program, Division of Public Health Science, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

PMID: 36934308
PMCID: PMC10025515
DOI: 10.1016/j.ygyno.2022.10.015

Abstract

Background: Limited data from prospective studies suggest that higher dietary intake of long-chain omega-3 polyunsaturated fatty acids (LCn3PUFA), which hold anti-inflammatory properties, may reduce endometrial cancer risk; particularly among certain subgroups characterized by body mass and tumor pathology.

Materials and methods: Data from 12 prospective cohort studies participating in the Epidemiology of Endometrial Cancer Consortium were harmonized as nested case-control studies, including 7268 endometrial cancer cases and 26,133 controls. Habitual diet was assessed by food frequency questionnaire, from which fatty acid intakes were estimated. Two-stage individual-participant data mixed effects meta-analysis estimated adjusted odds ratios (OR) and 95% confidence intervals (CI) through logistic regression for associations between study-specific energy-adjusted quartiles of LCn3PUFA and endometrial cancer risk.

Results: Women with the highest versus lowest estimated dietary intakes of docosahexaenoic acid, the most abundant LCn3PUFA in diet, had a 9% increased endometrial cancer risk (Quartile 4 vs. Quartile 1: OR 1.09, 95% CI: 1.01-1.19; P trend = 0.04). Similar elevated risks were observed for the summary measure of total LCn3PUFA (OR 1.07, 95% CI: 0.99-1.16; P trend = 0.06). Stratified by body mass index, higher intakes of LCn3PUFA were associated with 12-19% increased endometrial cancer risk among overweight/obese women and no increased risk among normal-weight women. Higher associations appeared restricted to White women. The results did not differ by cancer grade.

Conclusion: Higher dietary intakes of LCn3PUFA are unlikely to reduce endometrial cancer incidence; rather, they may be associated with small to moderate increases in risk in some subgroups of women, particularly overweight/obese women.

Keywords: Endometrial cancer; Fatty acid; Omega-3; Polyunsaturated; Uterine cancer.

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Conflict of interest statement

Author disclosures: PMW received honoraria from AstraZeneca for a presentation about diet, lifestyle, and ovarian cancer survival as part of an ovarian cancer symposium. The remaining authors have no conflicts of interest to report.

Figures

**Figure 1.**
Flowchart of sample selection from initial 17 E2C2 studies that made dietary data available.

See this image and copyright information in PMC

References

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Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis

Affiliations

Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis

Authors

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Abstract

Conflict of interest statement

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