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

Kliemann, Nathalie ; Ammar, Romain Ould ; Biessy, Carine ; Gicquiau, Audrey ; Katzke, Verena ; Kaaks, Rudolf ; Tjønneland, Anne ; Olsen, Anja ; Sánchez, Maria Jose and Crous-Bou, Marta , et al. (2022) In Cancer Epidemiology Biomarkers and Prevention 31(7). p.1359-1367
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... (More)

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.

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Contribution to journal
publication status
published
subject
in
Cancer Epidemiology Biomarkers and Prevention
volume
31
issue
7
pages
9 pages
publisher
American Association for Cancer Research
external identifiers
  • scopus:85133981163
  • pmid:35437568
ISSN
1055-9965
DOI
10.1158/1055-9965.EPI-22-0160
language
English
LU publication?
yes
id
51c3f164-09d8-4761-b724-94245089b768
date added to LUP
2022-10-10 14:27:06
date last changed
2024-06-13 13:08:03
@article{51c3f164-09d8-4761-b724-94245089b768,
  abstract     = {{<p>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; &lt;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)&lt;25 kg/m<sup>2</sup> or waist circumference (WC)&lt;80 cm or waist-to-hip ratio (WHR)&lt;0.8) and overweight (OW; BMI≥25 kg/m<sup>2</sup> 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 [OR<sub>WC</sub>, 1.48; 95% confidence interval (CI), 1.05–2.10 and OR<sub>WHR</sub>, 1.68; 95% CI, 1.21–2.35] and MU/OW (OR<sub>BMI</sub>, 2.38; 95% CI, 1.73–3.27; OR<sub>WC</sub>, 2.69; 95% CI, 1.92–3.77 and OR<sub>WHR</sub>, 1.83; 95% CI, 1.32–2.54). MH/OW individuals were also at increased endometrial cancer risk compared with MH/NW individuals (OR<sub>WC</sub>, 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.</p>}},
  author       = {{Kliemann, Nathalie and Ammar, Romain Ould and Biessy, Carine and Gicquiau, Audrey and Katzke, Verena and Kaaks, Rudolf and Tjønneland, Anne and Olsen, Anja and Sánchez, Maria Jose and Crous-Bou, Marta and Pasanisi, Fabrizio and Tin, Sandar Tin and Perez-Cornago, Aurora and Aune, Dagfinn and Christakoudi, Sofia and Heath, Alicia K. and Colorado-Yohar, Sandra M. and Grioni, Sara and Skeie, Guri and Sartor, Hanna and Idahl, Annika and Rylander, Charlotta and May, Anne M. and Weiderpass, Elisabete and Freisling, Heinz and Playdon, Mary C. and Rinaldi, Sabina and Murphy, Neil and Huybrechts, Inge and Dossus, Laure and Gunter, Marc J.}},
  issn         = {{1055-9965}},
  language     = {{eng}},
  number       = {{7}},
  pages        = {{1359--1367}},
  publisher    = {{American Association for Cancer Research}},
  series       = {{Cancer Epidemiology Biomarkers and Prevention}},
  title        = {{Metabolically Defined Body Size Phenotypes and Risk of Endometrial Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC)}},
  url          = {{http://dx.doi.org/10.1158/1055-9965.EPI-22-0160}},
  doi          = {{10.1158/1055-9965.EPI-22-0160}},
  volume       = {{31}},
  year         = {{2022}},
}