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

Theodore M. Brasky; Erinn M. Hade; David E. Cohn; Alison M. Newton; Stacey Petruzella; Kelli O'Connell; Kimberly A. Bertrand; Linda S. Cook; Immaculata De Vivo; Mengmeng Du; Jo L. Freudenheim; Christine M. Friedenreich; Marc T. Goodman; Jessica Gorzelitz; Torukiri I. Ibiebele; Vittorio Krogh; Linda M. Liao; Loren Lipworth; Lingeng Lu; Susan McCann; Tracy A. O'Mara; Julie R. Palmer; Jeanette Ponte; Anna Prizment; Harvey Risch; Sven Sandin; Leo J. Schouten; Veronica Wendy Setiawan; Xiao ou Shu; Britton Trabert; Piet A. van den Brandt; Penelope M. Webb; Nicolas Wentzensen; Lynne R. Wilkens; Alicja Wolk; Herbert Yu; Marian L. Neuhouser

doi:10.1016/j.ygyno.2022.10.015

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

Theodore M. Brasky, Erinn M. Hade, David E. Cohn, Alison M. Newton, Stacey Petruzella, Kelli O'Connell, Kimberly A. Bertrand, Linda S. Cook, Immaculata De Vivo, Mengmeng Du, Jo L. Freudenheim, Christine M. Friedenreich, Marc T. Goodman, Jessica Gorzelitz, Torukiri I. Ibiebele, Vittorio Krogh, Linda M. Liao, Loren Lipworth, Lingeng Lu, Susan McCannTracy A. O'Mara, Julie R. Palmer, Jeanette Ponte, Anna Prizment, Harvey Risch, Sven Sandin, Leo J. Schouten, Veronica Wendy Setiawan, Xiao ou Shu, Britton Trabert, Piet A. van den Brandt, Penelope M. Webb, Nicolas Wentzensen, Lynne R. Wilkens, Alicja Wolk, Herbert Yu, Marian L. Neuhouser

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

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.

Original language	English (US)
Pages (from-to)	137-146
Number of pages	10
Journal	Gynecologic oncology
Volume	169
DOIs	https://doi.org/10.1016/j.ygyno.2022.10.015
State	Published - Feb 2023

Bibliographical note

Funding Information:
This work is supported by National Cancer Institute of the United States grants R03CA212808 , P30CA008748 (Memorial Sloan Kettering NCI Support Grant), P30CA118100 , R01CA098346 , R01CA83918 , U01CA250476 , P01CA33619 , R01CA58598 , R01CA55700 , P20CA57113 , N01CN05223 , N01CN55424 , R01CA39742 , U01CA164973 , R03CA135632 , R01CA082838 , P01CA87969 , U01CA202979 , P30CA016056 , R01CA058420 , U01CA164974 , and R03CA169888 ; The Intramural Research Program of the National Cancer Institute of the United States project ZIA CP010196 ; National Cancer Institute of Canada grants 12018 , 13010 , 17323ACB , and 22190LSC ; The National Health and Medical Research Council of Australia grants APP1173346 , APP177524 , APP339435 , APP1073898 , APP1061341 , and APP1173170 ; Cancer Council Tasmania grants 403031 and 567636 ; Swedish Research Council grants 2015-03257 and 2017-00644 ; and the National Heart, Lung, and Blood Institute and U.S. Department of Health and Human Services grants HHSN2682011000046C , HSN268201100001C , HHSN268201100002C , HHSN268201100003C , and HHSN268201100004C .

Funding Information:
Swedish Mammography Cohort: The authors are thankful to the SMC participants. This research was [partly] supported by the Strategic Funds for the SMC from Karolinska Institute and Distinguished Professor Award to A. Wolk.

Funding Information:
NIH-AARP Diet and Health Study: This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute. https://dietandhealth.cancer.gov/acknowledgement.html .

Funding Information:
This work is supported by National Cancer Institute of the United States grants R03CA212808, P30CA008748 (Memorial Sloan Kettering NCI Support Grant), P30CA118100, R01CA098346, R01CA83918, U01CA250476, P01CA33619, R01CA58598, R01CA55700, P20CA57113, N01CN05223, N01CN55424, R01CA39742, U01CA164973, R03CA135632, R01CA082838, P01CA87969, U01CA202979, P30CA016056, R01CA058420, U01CA164974, and R03CA169888; The Intramural Research Program of the National Cancer Institute of the United States project ZIA CP010196; National Cancer Institute of Canada grants 12018, 13010, 17323ACB, and 22190LSC; The National Health and Medical Research Council of Australia grants APP1173346, APP177524, APP339435, APP1073898, APP1061341, and APP1173170; Cancer Council Tasmania grants 403031 and 567636; Swedish Research Council grants 2015-03257 and 2017-00644; and the National Heart, Lung, and Blood Institute and U.S. Department of Health and Human Services grants HHSN2682011000046C, HSN268201100001C, HHSN268201100002C, HHSN268201100003C, and HHSN268201100004C.Support for title page creation and format was provided by AuthorArranger, a tool developed by Mitchell Machiela and Geoffrey Tobias at the National Cancer Institute (https://authorarranger.nci.nih.gov). Alberta Endometrial Cancer and Physical Activity Study: The study was funded by the Canadian Cancer Society. C Friedenreich received career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research (AHFMR) during the conduct of this study. L Cook held a Canada Research Chair and received career award funding from AHFMR. Black Women's Health Study: Data on endometrial cancer pathology were obtained from several state cancer registries (AZ, CA, CO, CT, DE, DC, FL, GA, IL, IN, KY, LA, MD, MA, MI, NJ, NY, NC, OK, PA, SC, TN, TX, VA). The BWHS study protocol was approved by the Boston University Medical Campus Institutional Review Board (IRB) and by the IRBs of participating cancer registries as required. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, the National Institutes of Health, or the state cancer registries. We thank participants and staff of the BWHS for their contributions. Iowa Women's Health Study: The authors are thankful to the IWHS participants. We would also like to thank Ching-Ping Hong for consultation and assistance in data preparation. Netherlands Cohort Study on Diet and Cancer: The authors thank the participants of the Netherlands Cohort Study (NLCS) and further wish to thank the Netherlands Cancer Registry and the Dutch Pathology Registry. Additionally, NLCS staff members are acknowledged for their valuable assistance and advice. NIH-AARP Diet and Health Study: This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute. https://dietandhealth.cancer.gov/acknowledgement.html. Swedish Mammography Cohort: The authors are thankful to the SMC participants. This research was [partly] supported by the Strategic Funds for the SMC from Karolinska Institute and Distinguished Professor Award to A. Wolk. Women's Health Initiative: The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A listing of WHI investigators can be found at https://s3-us-west-2.amazonaws.com/www-whi-org/wp-content/uploads/WHI-Investigator-Short-List.pdf. Limited data from prospective studies suggest inverse associations between intakes of long-chain omega-3 fatty acids and endometrial cancer risk. Utilizing consortium data, we performed an individual-participant data meta-analysis to comprehensively examine these associations overall and in subgroups. We found that higher dietary intakes of long-chain omega-3 fatty acids 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.

Funding Information:
Alberta Endometrial Cancer and Physical Activity Study: The study was funded by the Canadian Cancer Society . C Friedenreich received career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research (AHFMR) during the conduct of this study. L Cook held a Canada Research Chair and received career award funding from AHFMR .

Publisher Copyright:
© 2022 Elsevier Inc.

Keywords

Endometrial cancer
Fatty acid
Omega-3
Polyunsaturated
Uterine cancer

PubMed: MeSH publication types

Meta-Analysis
Journal Article
Research Support, N.I.H., Intramural
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Publisher link

10.1016/j.ygyno.2022.10.015

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Cite this

Brasky, T. M., Hade, E. M., Cohn, D. E., Newton, A. M., Petruzella, S., O'Connell, K., Bertrand, K. A., Cook, L. S., De Vivo, I., Du, M., Freudenheim, J. L., Friedenreich, C. M., Goodman, M. T., Gorzelitz, J., Ibiebele, T. I., Krogh, V., Liao, L. M., Lipworth, L., Lu, L., ... Neuhouser, M. L. (2023). Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis. Gynecologic oncology, 169, 137-146. https://doi.org/10.1016/j.ygyno.2022.10.015

Brasky, TM, Hade, EM, Cohn, DE, Newton, AM, Petruzella, S, O'Connell, K, Bertrand, KA, Cook, LS, De Vivo, I, Du, M, Freudenheim, JL, Friedenreich, CM, Goodman, MT, Gorzelitz, J, Ibiebele, TI, Krogh, V, Liao, LM, Lipworth, L, Lu, L, McCann, S, O'Mara, TA, Palmer, JR, Ponte, J, Prizment, A, Risch, H, Sandin, S, Schouten, LJ, Setiawan, VW, Shu, XO, Trabert, B, van den Brandt, PA, Webb, PM, Wentzensen, N, Wilkens, LR, Wolk, A, Yu, H & Neuhouser, ML 2023, 'Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium: An individual-participant meta-analysis', Gynecologic oncology, vol. 169, pp. 137-146. https://doi.org/10.1016/j.ygyno.2022.10.015

@article{8681f8f844b645b48f108c423412a71d,

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

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",

author = "Brasky, {Theodore M.} and Hade, {Erinn M.} and Cohn, {David E.} and Newton, {Alison M.} and Stacey Petruzella and Kelli O'Connell and Bertrand, {Kimberly A.} and Cook, {Linda S.} and {De Vivo}, Immaculata and Mengmeng Du and Freudenheim, {Jo L.} and Friedenreich, {Christine M.} and Goodman, {Marc T.} and Jessica Gorzelitz and Ibiebele, {Torukiri I.} and Vittorio Krogh and Liao, {Linda M.} and Loren Lipworth and Lingeng Lu and Susan McCann and O'Mara, {Tracy A.} and Palmer, {Julie R.} and Jeanette Ponte and Anna Prizment and Harvey Risch and Sven Sandin and Schouten, {Leo J.} and Setiawan, {Veronica Wendy} and Shu, {Xiao ou} and Britton Trabert and {van den Brandt}, {Piet A.} and Webb, {Penelope M.} and Nicolas Wentzensen and Wilkens, {Lynne R.} and Alicja Wolk and Herbert Yu and Neuhouser, {Marian L.}",

note = "Funding Information: This work is supported by National Cancer Institute of the United States grants R03CA212808 , P30CA008748 (Memorial Sloan Kettering NCI Support Grant), P30CA118100 , R01CA098346 , R01CA83918 , U01CA250476 , P01CA33619 , R01CA58598 , R01CA55700 , P20CA57113 , N01CN05223 , N01CN55424 , R01CA39742 , U01CA164973 , R03CA135632 , R01CA082838 , P01CA87969 , U01CA202979 , P30CA016056 , R01CA058420 , U01CA164974 , and R03CA169888 ; The Intramural Research Program of the National Cancer Institute of the United States project ZIA CP010196 ; National Cancer Institute of Canada grants 12018 , 13010 , 17323ACB , and 22190LSC ; The National Health and Medical Research Council of Australia grants APP1173346 , APP177524 , APP339435 , APP1073898 , APP1061341 , and APP1173170 ; Cancer Council Tasmania grants 403031 and 567636 ; Swedish Research Council grants 2015-03257 and 2017-00644 ; and the National Heart, Lung, and Blood Institute and U.S. Department of Health and Human Services grants HHSN2682011000046C , HSN268201100001C , HHSN268201100002C , HHSN268201100003C , and HHSN268201100004C . Funding Information: Swedish Mammography Cohort: The authors are thankful to the SMC participants. This research was [partly] supported by the Strategic Funds for the SMC from Karolinska Institute and Distinguished Professor Award to A. Wolk. Funding Information: NIH-AARP Diet and Health Study: This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute. https://dietandhealth.cancer.gov/acknowledgement.html . Funding Information: This work is supported by National Cancer Institute of the United States grants R03CA212808, P30CA008748 (Memorial Sloan Kettering NCI Support Grant), P30CA118100, R01CA098346, R01CA83918, U01CA250476, P01CA33619, R01CA58598, R01CA55700, P20CA57113, N01CN05223, N01CN55424, R01CA39742, U01CA164973, R03CA135632, R01CA082838, P01CA87969, U01CA202979, P30CA016056, R01CA058420, U01CA164974, and R03CA169888; The Intramural Research Program of the National Cancer Institute of the United States project ZIA CP010196; National Cancer Institute of Canada grants 12018, 13010, 17323ACB, and 22190LSC; The National Health and Medical Research Council of Australia grants APP1173346, APP177524, APP339435, APP1073898, APP1061341, and APP1173170; Cancer Council Tasmania grants 403031 and 567636; Swedish Research Council grants 2015-03257 and 2017-00644; and the National Heart, Lung, and Blood Institute and U.S. Department of Health and Human Services grants HHSN2682011000046C, HSN268201100001C, HHSN268201100002C, HHSN268201100003C, and HHSN268201100004C.Support for title page creation and format was provided by AuthorArranger, a tool developed by Mitchell Machiela and Geoffrey Tobias at the National Cancer Institute (https://authorarranger.nci.nih.gov). Alberta Endometrial Cancer and Physical Activity Study: The study was funded by the Canadian Cancer Society. C Friedenreich received career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research (AHFMR) during the conduct of this study. L Cook held a Canada Research Chair and received career award funding from AHFMR. Black Women's Health Study: Data on endometrial cancer pathology were obtained from several state cancer registries (AZ, CA, CO, CT, DE, DC, FL, GA, IL, IN, KY, LA, MD, MA, MI, NJ, NY, NC, OK, PA, SC, TN, TX, VA). The BWHS study protocol was approved by the Boston University Medical Campus Institutional Review Board (IRB) and by the IRBs of participating cancer registries as required. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, the National Institutes of Health, or the state cancer registries. We thank participants and staff of the BWHS for their contributions. Iowa Women's Health Study: The authors are thankful to the IWHS participants. We would also like to thank Ching-Ping Hong for consultation and assistance in data preparation. Netherlands Cohort Study on Diet and Cancer: The authors thank the participants of the Netherlands Cohort Study (NLCS) and further wish to thank the Netherlands Cancer Registry and the Dutch Pathology Registry. Additionally, NLCS staff members are acknowledged for their valuable assistance and advice. NIH-AARP Diet and Health Study: This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute. https://dietandhealth.cancer.gov/acknowledgement.html. Swedish Mammography Cohort: The authors are thankful to the SMC participants. This research was [partly] supported by the Strategic Funds for the SMC from Karolinska Institute and Distinguished Professor Award to A. Wolk. Women's Health Initiative: The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A listing of WHI investigators can be found at https://s3-us-west-2.amazonaws.com/www-whi-org/wp-content/uploads/WHI-Investigator-Short-List.pdf. Limited data from prospective studies suggest inverse associations between intakes of long-chain omega-3 fatty acids and endometrial cancer risk. Utilizing consortium data, we performed an individual-participant data meta-analysis to comprehensively examine these associations overall and in subgroups. We found that higher dietary intakes of long-chain omega-3 fatty acids 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. Funding Information: Alberta Endometrial Cancer and Physical Activity Study: The study was funded by the Canadian Cancer Society . C Friedenreich received career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research (AHFMR) during the conduct of this study. L Cook held a Canada Research Chair and received career award funding from AHFMR . Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",

year = "2023",

month = feb,

doi = "10.1016/j.ygyno.2022.10.015",

language = "English (US)",

volume = "169",

pages = "137--146",

journal = "Gynecologic oncology",

issn = "0090-8258",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Dietary omega-3 fatty acids and endometrial cancer risk in the Epidemiology of Endometrial Cancer Consortium

T2 - An individual-participant meta-analysis

AU - Brasky, Theodore M.

AU - Hade, Erinn M.

AU - Cohn, David E.

AU - Newton, Alison M.

AU - Petruzella, Stacey

AU - O'Connell, Kelli

AU - Bertrand, Kimberly A.

AU - Cook, Linda S.

AU - De Vivo, Immaculata

AU - Du, Mengmeng

AU - Freudenheim, Jo L.

AU - Friedenreich, Christine M.

AU - Goodman, Marc T.

AU - Gorzelitz, Jessica

AU - Ibiebele, Torukiri I.

AU - Krogh, Vittorio

AU - Liao, Linda M.

AU - Lipworth, Loren

AU - Lu, Lingeng

AU - McCann, Susan

AU - O'Mara, Tracy A.

AU - Palmer, Julie R.

AU - Ponte, Jeanette

AU - Prizment, Anna

AU - Risch, Harvey

AU - Sandin, Sven

AU - Schouten, Leo J.

AU - Setiawan, Veronica Wendy

AU - Shu, Xiao ou

AU - Trabert, Britton

AU - van den Brandt, Piet A.

AU - Webb, Penelope M.

AU - Wentzensen, Nicolas

AU - Wilkens, Lynne R.

AU - Wolk, Alicja

AU - Yu, Herbert

AU - Neuhouser, Marian L.

N1 - Funding Information: This work is supported by National Cancer Institute of the United States grants R03CA212808 , P30CA008748 (Memorial Sloan Kettering NCI Support Grant), P30CA118100 , R01CA098346 , R01CA83918 , U01CA250476 , P01CA33619 , R01CA58598 , R01CA55700 , P20CA57113 , N01CN05223 , N01CN55424 , R01CA39742 , U01CA164973 , R03CA135632 , R01CA082838 , P01CA87969 , U01CA202979 , P30CA016056 , R01CA058420 , U01CA164974 , and R03CA169888 ; The Intramural Research Program of the National Cancer Institute of the United States project ZIA CP010196 ; National Cancer Institute of Canada grants 12018 , 13010 , 17323ACB , and 22190LSC ; The National Health and Medical Research Council of Australia grants APP1173346 , APP177524 , APP339435 , APP1073898 , APP1061341 , and APP1173170 ; Cancer Council Tasmania grants 403031 and 567636 ; Swedish Research Council grants 2015-03257 and 2017-00644 ; and the National Heart, Lung, and Blood Institute and U.S. Department of Health and Human Services grants HHSN2682011000046C , HSN268201100001C , HHSN268201100002C , HHSN268201100003C , and HHSN268201100004C . Funding Information: Swedish Mammography Cohort: The authors are thankful to the SMC participants. This research was [partly] supported by the Strategic Funds for the SMC from Karolinska Institute and Distinguished Professor Award to A. Wolk. Funding Information: NIH-AARP Diet and Health Study: This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute. https://dietandhealth.cancer.gov/acknowledgement.html . Funding Information: This work is supported by National Cancer Institute of the United States grants R03CA212808, P30CA008748 (Memorial Sloan Kettering NCI Support Grant), P30CA118100, R01CA098346, R01CA83918, U01CA250476, P01CA33619, R01CA58598, R01CA55700, P20CA57113, N01CN05223, N01CN55424, R01CA39742, U01CA164973, R03CA135632, R01CA082838, P01CA87969, U01CA202979, P30CA016056, R01CA058420, U01CA164974, and R03CA169888; The Intramural Research Program of the National Cancer Institute of the United States project ZIA CP010196; National Cancer Institute of Canada grants 12018, 13010, 17323ACB, and 22190LSC; The National Health and Medical Research Council of Australia grants APP1173346, APP177524, APP339435, APP1073898, APP1061341, and APP1173170; Cancer Council Tasmania grants 403031 and 567636; Swedish Research Council grants 2015-03257 and 2017-00644; and the National Heart, Lung, and Blood Institute and U.S. Department of Health and Human Services grants HHSN2682011000046C, HSN268201100001C, HHSN268201100002C, HHSN268201100003C, and HHSN268201100004C.Support for title page creation and format was provided by AuthorArranger, a tool developed by Mitchell Machiela and Geoffrey Tobias at the National Cancer Institute (https://authorarranger.nci.nih.gov). Alberta Endometrial Cancer and Physical Activity Study: The study was funded by the Canadian Cancer Society. C Friedenreich received career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research (AHFMR) during the conduct of this study. L Cook held a Canada Research Chair and received career award funding from AHFMR. Black Women's Health Study: Data on endometrial cancer pathology were obtained from several state cancer registries (AZ, CA, CO, CT, DE, DC, FL, GA, IL, IN, KY, LA, MD, MA, MI, NJ, NY, NC, OK, PA, SC, TN, TX, VA). The BWHS study protocol was approved by the Boston University Medical Campus Institutional Review Board (IRB) and by the IRBs of participating cancer registries as required. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Cancer Institute, the National Institutes of Health, or the state cancer registries. We thank participants and staff of the BWHS for their contributions. Iowa Women's Health Study: The authors are thankful to the IWHS participants. We would also like to thank Ching-Ping Hong for consultation and assistance in data preparation. Netherlands Cohort Study on Diet and Cancer: The authors thank the participants of the Netherlands Cohort Study (NLCS) and further wish to thank the Netherlands Cancer Registry and the Dutch Pathology Registry. Additionally, NLCS staff members are acknowledged for their valuable assistance and advice. NIH-AARP Diet and Health Study: This research was supported [in part] by the Intramural Research Program of the NIH, National Cancer Institute. https://dietandhealth.cancer.gov/acknowledgement.html. Swedish Mammography Cohort: The authors are thankful to the SMC participants. This research was [partly] supported by the Strategic Funds for the SMC from Karolinska Institute and Distinguished Professor Award to A. Wolk. Women's Health Initiative: The authors thank the WHI investigators and staff for their dedication, and the study participants for making the program possible. A listing of WHI investigators can be found at https://s3-us-west-2.amazonaws.com/www-whi-org/wp-content/uploads/WHI-Investigator-Short-List.pdf. Limited data from prospective studies suggest inverse associations between intakes of long-chain omega-3 fatty acids and endometrial cancer risk. Utilizing consortium data, we performed an individual-participant data meta-analysis to comprehensively examine these associations overall and in subgroups. We found that higher dietary intakes of long-chain omega-3 fatty acids 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. Funding Information: Alberta Endometrial Cancer and Physical Activity Study: The study was funded by the Canadian Cancer Society . C Friedenreich received career awards from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research (AHFMR) during the conduct of this study. L Cook held a Canada Research Chair and received career award funding from AHFMR . Publisher Copyright: © 2022 Elsevier Inc.

PY - 2023/2

Y1 - 2023/2

N2 - 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.

AB - 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.

KW - Endometrial cancer

KW - Fatty acid

KW - Omega-3

KW - Polyunsaturated

KW - Uterine cancer

UR - http://www.scopus.com/inward/record.url?scp=85140964314&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85140964314&partnerID=8YFLogxK

U2 - 10.1016/j.ygyno.2022.10.015

DO - 10.1016/j.ygyno.2022.10.015

M3 - Article

C2 - 36934308

AN - SCOPUS:85140964314

SN - 0090-8258

VL - 169

SP - 137

EP - 146

JO - Gynecologic oncology

JF - Gynecologic oncology

ER -

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

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