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Cancer Epidemiology, Biomarkers & Prevention
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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

Melissa A. Merritt, Ioanna Tzoulaki, Shelley S. Tworoger, Immaculata De Vivo, Susan E. Hankinson, Judy Fernandes, Konstantinos K. Tsilidis, Elisabete Weiderpass, Anne Tjønneland, Kristina E.N. Petersen, Christina C. Dahm, Kim Overvad, Laure Dossus, Marie-Christine Boutron-Ruault, Guy Fagherazzi, Renée T. Fortner, Rudolf Kaaks, Krasimira Aleksandrova, Heiner Boeing, Antonia Trichopoulou, Christina Bamia, Dimitrios Trichopoulos, Domenico Palli, Sara Grioni, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, H.B(as). Bueno-de-Mesquita, N. Charlotte Onland-Moret, Petra H. Peeters, Inger T. Gram, Guri Skeie, J. Ramón Quirós, Eric J. Duell, María-José Sánchez, D. Salmerón, Aurelio Barricarte, Saioa Chamosa, Ulrica Ericson, Emily Sonestedt, Lena Maria Nilsson, Annika Idahl, Kay-Tee Khaw, Nicholas Wareham, Ruth C. Travis, Sabina Rinaldi, Isabelle Romieu, Chirag J. Patel, Elio Riboli and Marc J. Gunter
Melissa A. Merritt
1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
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  • For correspondence: m.merritt@imperial.ac.uk
Ioanna Tzoulaki
1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
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Shelley S. Tworoger
2Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
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Immaculata De Vivo
2Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
4Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts.
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Susan E. Hankinson
2Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
5Division of Biostatistics and Epidemiology, University of Massachusetts, Amherst, Massachusetts.
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Judy Fernandes
1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
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Konstantinos K. Tsilidis
6Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece.
7Cancer Epidemiology Unit, University of Oxford, Oxford, United Kingdom.
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Elisabete Weiderpass
8Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
9Department of Research, Cancer Registry of Norway, Oslo, Norway.
10Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
11Department of Genetic Epidemiology, Samfundet Folkhälsan, Helsinki, Finland.
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Anne Tjønneland
12Danish Cancer Society Research Center, Copenhagen, Denmark.
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Kristina E.N. Petersen
12Danish Cancer Society Research Center, Copenhagen, Denmark.
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Christina C. Dahm
13Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
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Kim Overvad
13Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
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Laure Dossus
14Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.
15University Paris Sud, Villejuif, France.
16IGR, Villejuif, France.
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Marie-Christine Boutron-Ruault
14Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.
15University Paris Sud, Villejuif, France.
16IGR, Villejuif, France.
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Guy Fagherazzi
14Inserm, Centre for Research in Epidemiology and Population Health (CESP), Villejuif, France.
15University Paris Sud, Villejuif, France.
16IGR, Villejuif, France.
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Renée T. Fortner
17Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Rudolf Kaaks
17Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.
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Krasimira Aleksandrova
18Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
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Heiner Boeing
18Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
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Antonia Trichopoulou
19Hellenic Health Foundation, Athens, Greece.
20Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
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Christina Bamia
21Department of Hygiene, Epidemiology, and Medical Statistics, University of Athens Medical School, Athens, Greece.
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Dimitrios Trichopoulos
3Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts.
19Hellenic Health Foundation, Athens, Greece.
20Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece.
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Domenico Palli
22Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute—ISPO, Florence, Italy.
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Sara Grioni
23Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy.
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Rosario Tumino
24Cancer Registry and Histopathology Unit, “Civic–M.P. Arezzo” Hospital, ASP, Ragusa, Italy.
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Carlotta Sacerdote
25Unit of Cancer Epidemiology, AO Citta' della Salute e della Scienza–University of Turin and Center for Cancer Prevention (CPO-Piemonte), Turin, Italy.
26Human Genetics Foundation (HuGeF), Turin, Italy.
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Amalia Mattiello
27Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.
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H.B(as). Bueno-de-Mesquita
1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
28Department for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands.
29Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, the Netherlands.
30Department of Social and Preventive Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
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N. Charlotte Onland-Moret
31Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.
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Petra H. Peeters
1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
31Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, the Netherlands.
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Inger T. Gram
8Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
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Guri Skeie
8Department of Community Medicine, Faculty of Health Sciences, University of Tromsø, The Arctic University of Norway, Tromsø, Norway.
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J. Ramón Quirós
32Public Health Directorate, Asturias, Spain.
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Eric J. Duell
33Unit of Nutrition, Environment, and Cancer, Cancer Epidemiology Research Program, Bellvitge Biomedical Research Institute (IDIBELL), Catalan Institute of Oncology (ICO), Barcelona, Spain.
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María-José Sánchez
34Escuela Andaluza de Salud Pública, Instituto de Investigación Biosanitaria de Granada (Granada.ibs), Granada, Spain.
35CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
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D. Salmerón
35CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
36Department of Epidemiology, Murcia Regional Health Council, Murcia, Spain.
37Department of Health and Social Sciences, Universidad de Murcia, Murcia, Spain.
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Aurelio Barricarte
35CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.
38Navarre Public Health Institute, Pamplona, Spain.
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Saioa Chamosa
39Public Health Department of Gipuzkoa, Government of the Basque Country, San Sebastian, Spain.
40BioDonostia Research Institute, San Sebastian, Spain.
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Ulrica Ericson
41Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
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Emily Sonestedt
41Department of Clinical Sciences in Malmö, Lund University, Malmö, Sweden.
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Lena Maria Nilsson
42Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.
43Arcum, Arctic Research Centre at Umeå University, Umeå, Sweden.
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Annika Idahl
44Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.
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Kay-Tee Khaw
45University of Cambridge, School of Clinical Medicine, Cambridge, United Kingdom.
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Nicholas Wareham
46MRC Epidemiology Unit, University of Cambridge, Cambridge, United Kingdom.
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Ruth C. Travis
47Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom.
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Sabina Rinaldi
48International Agency for Research on Cancer, Lyon, France.
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Isabelle Romieu
48International Agency for Research on Cancer, Lyon, France.
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Chirag J. Patel
49Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts.
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Elio Riboli
1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
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Marc J. Gunter
1Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.
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DOI: 10.1158/1055-9965.EPI-14-0970 Published February 2015
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Abstract

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. Cancer Epidemiol Biomarkers Prev; 24(2); 466–71. ©2015 AACR.

Footnotes

  • Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/).

  • Received August 21, 2014.
  • Revision received November 3, 2014.
  • Accepted November 3, 2014.
  • ©2015 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 24 (2)
February 2015
Volume 24, Issue 2
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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
Melissa A. Merritt, Ioanna Tzoulaki, Shelley S. Tworoger, Immaculata De Vivo, Susan E. Hankinson, Judy Fernandes, Konstantinos K. Tsilidis, Elisabete Weiderpass, Anne Tjønneland, Kristina E.N. Petersen, Christina C. Dahm, Kim Overvad, Laure Dossus, Marie-Christine Boutron-Ruault, Guy Fagherazzi, Renée T. Fortner, Rudolf Kaaks, Krasimira Aleksandrova, Heiner Boeing, Antonia Trichopoulou, Christina Bamia, Dimitrios Trichopoulos, Domenico Palli, Sara Grioni, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, H.B(as). Bueno-de-Mesquita, N. Charlotte Onland-Moret, Petra H. Peeters, Inger T. Gram, Guri Skeie, J. Ramón Quirós, Eric J. Duell, María-José Sánchez, D. Salmerón, Aurelio Barricarte, Saioa Chamosa, Ulrica Ericson, Emily Sonestedt, Lena Maria Nilsson, Annika Idahl, Kay-Tee Khaw, Nicholas Wareham, Ruth C. Travis, Sabina Rinaldi, Isabelle Romieu, Chirag J. Patel, Elio Riboli and Marc J. Gunter
Cancer Epidemiol Biomarkers Prev February 1 2015 (24) (2) 466-471; DOI: 10.1158/1055-9965.EPI-14-0970

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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
Melissa A. Merritt, Ioanna Tzoulaki, Shelley S. Tworoger, Immaculata De Vivo, Susan E. Hankinson, Judy Fernandes, Konstantinos K. Tsilidis, Elisabete Weiderpass, Anne Tjønneland, Kristina E.N. Petersen, Christina C. Dahm, Kim Overvad, Laure Dossus, Marie-Christine Boutron-Ruault, Guy Fagherazzi, Renée T. Fortner, Rudolf Kaaks, Krasimira Aleksandrova, Heiner Boeing, Antonia Trichopoulou, Christina Bamia, Dimitrios Trichopoulos, Domenico Palli, Sara Grioni, Rosario Tumino, Carlotta Sacerdote, Amalia Mattiello, H.B(as). Bueno-de-Mesquita, N. Charlotte Onland-Moret, Petra H. Peeters, Inger T. Gram, Guri Skeie, J. Ramón Quirós, Eric J. Duell, María-José Sánchez, D. Salmerón, Aurelio Barricarte, Saioa Chamosa, Ulrica Ericson, Emily Sonestedt, Lena Maria Nilsson, Annika Idahl, Kay-Tee Khaw, Nicholas Wareham, Ruth C. Travis, Sabina Rinaldi, Isabelle Romieu, Chirag J. Patel, Elio Riboli and Marc J. Gunter
Cancer Epidemiol Biomarkers Prev February 1 2015 (24) (2) 466-471; DOI: 10.1158/1055-9965.EPI-14-0970
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