Folate Intake and Ovarian Cancer Risk among Women with Endometriosis: A Case–Control Study from the Ovarian Cancer Association Consortium

Author:

Gersekowski Kate1ORCID,Ibiebele Torukiri I1ORCID,Doherty Jennifer A.2ORCID,Harris Holly R.34ORCID,Goodman Marc T.56ORCID,Terry Kathryn L.78ORCID,Wu Anna H.9ORCID,Bandera Elisa V.10ORCID,Qin Bo10ORCID,Ong Jue-Sheng11ORCID,Tyrer Jonathan P.12ORCID,Dixon-Suen Suzanne C.1314ORCID,Modugno Francesmary151617ORCID,Risch Harvey A18ORCID,Webb Penelope M.119ORCID,

Affiliation:

1. 1Gynaecological Cancers Group, Population Health Program, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

2. 2Huntsman Cancer Institute, Department of Population Health Sciences, University of Utah, Salt Lake City, Utah.

3. 3Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington.

4. 4Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.

5. 5Cancer Prevention and Control Program, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.

6. 6Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.

7. 7Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.

8. 8Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

9. 9Department of Population and Public Health, Keck School of Medicine, University of Southern California, Los Angeles, California.

10. 10Cancer Epidemiology and Health Outcomes, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey.

11. 11Statistical Genetics Lab, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia.

12. 12Department of Oncology, University of Cambridge, Cambridge, UK.

13. 13Institute for Physical Activity and Nutrition, School of Exercise and Nutrition Sciences, Deakin University, Geelong, Victoria, Australia.

14. 14Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.

15. 15Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pittsburgh, Pennsylvania.

16. 16Division of Gynecologic Oncology, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

17. 17Women's Cancer Research Center, Magee-Womens Research Institute and Hillman Cancer Center, Pittsburgh, Pennsylvania.

18. 18Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut.

19. 19University of Queensland, School of Public Health, Brisbane, Queensland, Australia.

Abstract

Abstract Background: Although folate intake has not been associated with an increased risk of ovarian cancer overall, studies of other cancer types have suggested that high folate intake may promote carcinogenesis in precancerous lesions. Women with endometriosis (a potential precancerous lesion) have an increased risk of developing ovarian cancer; however, whether high folate intake increases risk in this group is unknown. Methods: We conducted a pooled analysis of six case–control studies from the Ovarian Cancer Association Consortium to investigate the association between folate intake and risk of ovarian cancer among women with and without self-reported endometriosis. We included 570 cases/558 controls with and 5,171/7,559 without endometriosis. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals for the association between folate intake (dietary, supplemental, and total) and ovarian cancer risk. Finally, we used Mendelian randomization (MR) to evaluate our results using genetic markers as a proxy for folate status. Results: Higher dietary folate intake was associated with an increased risk of ovarian cancer for women with endometriosis [OR, 1.37 (1.01–1.86)] but not for women without endometriosis. There was no association between supplemental folate intake and ovarian cancer risk for women with or without endometriosis. A similar pattern was seen using MR. Conclusions: High dietary folate intake may be associated with an increased risk of ovarian cancer among women with endometriosis. Impact: Women with endometriosis with high folate diets may be at increased risk of ovarian cancer. Further research is needed on the potential cancer-promoting effects of folate in this group.

Funder

Ovarian Cancer Research Fund

National Institutes of Health

Canadian Institutes of Health Research

European Commission's Seventh Framework Programme

US National Cancer Institute GAME-ON Post-GWAS Initiative

Wellcome Trust

National Health and Medical Research Council

U.S. Army Medical Research and Materiel Command

California Cancer Research Program

U.S. Department of Defense

National Cancer Institute

Rutgers Cancer Institute of New Jersey

Department Of Defense Congressionally Directed Medical Research Programs

Publisher

American Association for Cancer Research (AACR)

Subject

Oncology,Epidemiology

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