Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Reference-Cited by-同舟云学术

Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)

Published:2022-04-18 Issue:7 Volume:31 Page:1359-1367
ISSN:1055-9965
Container-title:Cancer Epidemiology, Biomarkers & Prevention
language:en
Short-container-title:

Author:

Kliemann Nathalie¹^ORCID,Ould Ammar Romain¹^ORCID,Biessy Carine¹^ORCID,Gicquiau Audrey¹,Katzke Verena²^ORCID,Kaaks Rudolf²^ORCID,Tjønneland Anne³⁴,Olsen Anja⁴⁵^ORCID,Sánchez Maria-Jose⁶⁷⁸⁹^ORCID,Crous-Bou Marta¹⁰¹¹,Pasanisi Fabrizio¹²,Tin Tin Sandar¹³,Perez-Cornago Aurora¹³^ORCID,Aune Dagfinn¹⁴¹⁵¹⁶^ORCID,Christakoudi Sofia¹⁴¹⁷,Heath Alicia K.¹⁴^ORCID,Colorado-Yohar Sandra M.⁸¹⁸¹⁹,Grioni Sara²⁰^ORCID,Skeie Guri²¹^ORCID,Sartor Hanna²²^ORCID,Idahl Annika²³^ORCID,Rylander Charlotta²¹,May Anne M.²⁴,Weiderpass Elisabete¹^ORCID,Freisling Heinz¹^ORCID,Playdon Mary C.²⁵²⁶^ORCID,Rinaldi Sabina¹,Murphy Neil¹,Huybrechts Inge¹^ORCID,Dossus Laure¹^ORCID,Gunter Marc J.¹^ORCID

Affiliation:

1. 1International Agency for Research on Cancer, Lyon, France.

2. 2Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

3. 3Danish Cancer Society Research Center, Copenhagen, Denmark.

4. 4Department of Public Health, University of Copenhagen, Copenhagen, Denmark.

5. 5Department of Public Health, Aarhus University, Aarhus, Denmark.

6. 6Escuela Andaluza de Salud Pública (EASP), Granada, Spain.

7. 7Instituto de Investigación Biosanitaria ibs, GRANADA, Granada, Spain.

8. 8Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain.

9. 9Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain.

10. 10Unit of Nutrition and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology (ICO)—Bellvitge Biomedical Research Institute (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain.

11. 11Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

12. 12Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy.

13. 13Nuffield Department of Population Health, Cancer Epidemiology Unit, University of Oxford, Oxford, England.

14. 14Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom.

15. 15Department of Nutrition, Oslo New University College, Oslo, Norway.

16. 16Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway.

17. 17Department of Inflammation Biology, King's College London, London, United Kingdom.

18. 18Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.

19. 19Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.

20. 20Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Italy.

21. 21Department of Community Medicine, UIT—The Arctic University of Norway, Tromsø, Norway.

22. 22Diagnostic Radiology, Lund University, Lund, Sweden.

23. 23Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, Umeå, Sweden.

24. 24Julius Center for Health Sciences and Primary care, University Medical Center Utrecht, Utrecht, the Netherlands.

25. 25Department of Nutrition and Integrative Physiology, University of Utah, Salt Lake City, Utah.

26. 26Cancer Control and Population Sciences, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.

Abstract

Abstract Background: Obesity is a risk factor for endometrial cancer but whether metabolic dysfunction is associated with endometrial cancer independent of body size is not known. Methods: The association of metabolically defined body size phenotypes with endometrial cancer risk was investigated in a nested case–control study (817 cases/ 817 controls) within the European Prospective Investigation into Cancer and Nutrition (EPIC). Concentrations of C-peptide were used to define metabolically healthy (MH; <1st tertile) and metabolically unhealthy (MU; ≥1st tertile) status among the control participants. These metabolic health definitions were combined with normal weight (NW); body mass index (BMI)<25 kg/m2 or waist circumference (WC)<80 cm or waist-to-hip ratio (WHR)<0.8) and overweight (OW; BMI≥25 kg/m2 or WC≥80 cm or WHR≥0.8) status, generating four phenotype groups for each anthropometric measure: (i) MH/NW, (ii) MH/OW, (iii) MU/NW, and (iv) MU/OW. Results: In a multivariable-adjusted conditional logistic regression model, compared with MH/NW individuals, endometrial cancer risk was higher among those classified as MU/NW [ORWC, 1.48; 95% confidence interval (CI), 1.05–2.10 and ORWHR, 1.68; 95% CI, 1.21–2.35] and MU/OW (ORBMI, 2.38; 95% CI, 1.73–3.27; ORWC, 2.69; 95% CI, 1.92–3.77 and ORWHR, 1.83; 95% CI, 1.32–2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (ORWC, 1.94; 95% CI, 1.24–3.04). Conclusions: Women with metabolic dysfunction appear to have higher risk of endometrial cancer regardless of their body size. However, OW status raises endometrial cancer risk even among women with lower insulin levels, suggesting that obesity-related pathways are relevant for the development of this cancer beyond insulin. Impact: Classifying women by metabolic health may be of greater utility in identifying those at higher risk for endometrial cancer than anthropometry per se.

Funder

World Cancer Research Fund

Statistics Netherlands

Health Research Fund

Instituto de Salud Carlos III

Regional Governments of Andalucía

Asturias

Basque Country

Murcia and Navarra

Catalan Institute of Oncology

Swedish Cancer Society

Swedish Research Council