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

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  • Nathalie Kliemann
  • Romain Ould Ammar
  • Carine Biessy
  • Audrey Gicquiau
  • Verena Katzke
  • Rudolf Kaaks
  • Anja Olsen
  • Maria-Jose Sanchez
  • Marta Crous-Bou
  • Fabrizio Pasanisi
  • Sandar Tin Tin
  • Aurora Perez-Cornago
  • Dagfinn Aune
  • Sofia Christakoudi
  • Alicia K. Heath
  • Sandra M. Colorado-Yohar
  • Sara Grioni
  • Guri Skeie
  • Hanna Sartor
  • Annika Idahl
  • Charlotta Rylander
  • Anne M. May
  • Elisabete Weiderpass
  • Heinz Freisling
  • Mary C. Playdon
  • Sabina Rinaldi
  • Neil Murphy
  • Inge Huybrechts
  • Laure Dossus
  • Marc J. Gunter

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.

Original languageEnglish
JournalCancer Epidemiology, Biomarkers & Prevention
Volume31
Issue number7
Pages (from-to)1359-1367
Number of pages9
ISSN1055-9965
DOIs
Publication statusPublished - 2022

    Research areas

  • INSULIN-RESISTANCE, MASS INDEX, ANTHROPOMETRIC FACTORS, C-PEPTIDE, OBESITY, HEALTH, OVERWEIGHT, ESTROGEN, VALIDITY, GROWTH

ID: 314896351