TY - JOUR
T1 - Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)
AU - Kliemann, Nathalie
AU - Ammar, Romain Ould
AU - Biessy, Carine
AU - Gicquiau, Audrey
AU - Katzke, Verena
AU - Kaaks, Rudolf
AU - Tjønneland, Anne
AU - Olsen, Anja
AU - Sánchez, Maria Jose
AU - Crous-Bou, Marta
AU - Pasanisi, Fabrizio
AU - Tin, Sandar Tin
AU - Perez-Cornago, Aurora
AU - Aune, Dagfinn
AU - Christakoudi, Sofia
AU - Heath, Alicia K.
AU - Colorado-Yohar, Sandra M.
AU - Grioni, Sara
AU - Skeie, Guri
AU - Sartor, Hanna
AU - Idahl, Annika
AU - Rylander, Charlotta
AU - May, Anne M.
AU - Weiderpass, Elisabete
AU - Freisling, Heinz
AU - Playdon, Mary C.
AU - Rinaldi, Sabina
AU - Murphy, Neil
AU - Huybrechts, Inge
AU - Dossus, Laure
AU - Gunter, Marc J.
N1 - Funding Information:
The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London that has additional infrastructure support provided by the NIHR Imperial Biomedical Research Center (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l’Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM; France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition PotsdamRehbruecke (DIfE), Federal Ministry of Education and Research (BMBF; Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF—ERC-2009-AdG 232997), Statistics Netherlands (the Netherlands); Health Research Fund (FIS)—Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology—ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Ska° ne and V€asterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford, United Kingdom). This work was supported by a grant from Cancer Research UK (C19335/ A21351; to M.J. Gunter).
Funding Information:
The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and also by the Department of Epidemiology
Funding Information:
S. Tin Tin reports grants from Health Research Council of New Zealand during the conduct of the study. A.M. May reports grants from Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland, the Netherlands) during the conduct of the study. No disclosures were reported by the other authors.
Publisher Copyright:
©2022 The Authors; Published by the American Association for Cancer Research
PY - 2022/7
Y1 - 2022/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85133981163&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-22-0160
DO - 10.1158/1055-9965.EPI-22-0160
M3 - Article
C2 - 35437568
AN - SCOPUS:85133981163
SN - 1055-9965
VL - 31
SP - 1359
EP - 1367
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -