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.
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.
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 -
