Article open access publication

Investigation of Dietary Factors and Endometrial Cancer Risk Using a Nutrient-wide Association Study Approach in the EPIC and Nurses' Health Study (NHS) and NHSII

Cancer Epidemiology Biomarkers & Prevention, American Association for Cancer Research (AACR), ISSN 1055-9965

Volume 24, 2, 2015

DOI:10.1158/1055-9965.epi-14-0970, Dimensions: pub.1017936622, PMC: PMC4324546, PMID: 25662427,



  1. (1) Imperial College London, grid.7445.2
  2. (2) Brigham and Women's Hospital, grid.62560.37
  3. (3) University of Warwick, grid.7372.1
  4. (4) Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway. Department of Research, Cancer Registry of Norway, Oslo, Norway. Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. Department of Genetic Epidemiology, Samfundet Folkhälsan, Helsinki, Finland.
  5. (5) Danish Cancer Society, grid.417390.8
  6. (6) Aarhus University, grid.7048.b, AU
  7. (7) Centre for research in epidemiology and population health, grid.463845.8
  8. (8) German Cancer Research Center, grid.7497.d
  9. (9) German Institute of Human Nutrition, grid.418213.d
  10. (10) Hellenic Health Foundation, grid.424637.0
  11. (11) National and Kapodistrian University of Athens, grid.5216.0
  12. (12) Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts. Hellenic Health Foundation, Athens, Greece. Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
  13. (13) Istituto per lo Studio e la Prevenzione Oncologica, grid.417623.5
  14. (14) Fondazione IRCCS Istituto Nazionale dei Tumori, grid.417893.0
  15. (15) Cancer Registry and Histopathology Unit, "Civic M.P. Arezzo" Hospital, ASP, Ragusa, Italy.
  16. (16) Piedmont Reference Center for Epidemiology and Cancer Prevention, grid.420240.0
  17. (17) University of Naples Federico II, grid.4691.a
  18. (18) Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands. Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands. Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
  19. (19) University Medical Center Utrecht, grid.7692.a
  20. (20) Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom. Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.
  21. (21) The Arctic University of Norway, grid.10919.30
  22. (22) Public Health Directorate, Asturias, Spain.
  23. (23) Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.
  24. (24) Andalusian School of Public Health, grid.413740.5
  25. (25) Institute of Health Carlos III, grid.413448.e
  26. (26) Public Health Department of Gipuzkoa, Government of the Basque Country, San Sebastian, Spain. BioDonostia Research Institute, San Sebastian, Spain.
  27. (27) Lund University, grid.4514.4
  28. (28) Umeå University, grid.12650.30
  29. (29) University of Cambridge, grid.5335.0
  30. (30) University of Oxford, grid.4991.5
  31. (31) International Agency For Research On Cancer, grid.17703.32
  32. (32) Harvard University, grid.38142.3c


Data on the role of dietary factors in endometrial cancer development are limited and inconsistent. We applied a "nutrient-wide association study" approach to systematically evaluate dietary risk associations for endometrial cancer while controlling for multiple hypothesis tests using the false discovery rate (FDR) and validating the results in an independent cohort. We evaluated endometrial cancer risk associations for dietary intake of 84 foods and nutrients based on dietary questionnaires in three prospective studies, the European Prospective Investigation into Cancer and Nutrition (EPIC; N = 1,303 cases) followed by validation of nine foods/nutrients (FDR ≤ 0.10) in the Nurses' Health Studies (NHS/NHSII; N = 1,531 cases). Cox regression models were used to estimate HRs and 95% confidence intervals (CI). In multivariate adjusted comparisons of the extreme categories of intake at baseline, coffee was inversely associated with endometrial cancer risk (EPIC, median intake 750 g/day vs. 8.6; HR, 0.81; 95% CI, 0.68-0.97, Ptrend = 0.09; NHS/NHSII, median intake 1067 g/day vs. none; HR, 0.82; 95% CI, 0.70-0.96, Ptrend = 0.04). Eight other dietary factors that were associated with endometrial cancer risk in the EPIC study (total fat, monounsaturated fat, carbohydrates, phosphorus, butter, yogurt, cheese, and potatoes) were not confirmed in the NHS/NHSII. Our findings suggest that coffee intake may be inversely associated with endometrial cancer risk. Further data are needed to confirm these findings and to examine the mechanisms linking coffee intake to endometrial cancer risk to develop improved prevention strategies.


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