TY - JOUR
T1 - Adiposity and endometrial cancer risk in postmenopausal women
T2 - A sequential causal mediation analysis
AU - Dashti, S. Ghazaleh
AU - English, Dallas R.
AU - Simpson, Julie A.
AU - Karahalios, Amalia
AU - Moreno-Betancur, Margarita
AU - Biessy, Carine
AU - Rinaldi, Sabina
AU - Ferrari, Pietro
AU - Tjønneland, Anne
AU - Halkjær, Jytte
AU - Dahm, Christina C.
AU - Vistisen, Helene Tilma
AU - Menegaux, Florence
AU - Perduca, Vittorio
AU - Severi, Gianluca
AU - Aleksandrova, Krasimira
AU - Schulze, Matthias B.
AU - Masala, Giovanna
AU - Sieri, Sabina
AU - Tumino, Rosario
AU - Macciotta, Alessandra
AU - Panico, Salvatore
AU - Hiensch, Anouk E.
AU - May, Anne M.
AU - Quirós, J. Ramón
AU - Agudo, Antonio
AU - Sánchez, Maria Jose
AU - Amiano, Pilar
AU - Colorado-Yohar, Sandra
AU - Ardanaz, Eva
AU - Allen, Naomi E.
AU - Weiderpass, Elisabete
AU - Fortner, Renée Turzanski
AU - Christakoudi, Sofia
AU - Tsilidis, Konstantinos K.
AU - Riboli, Elio
AU - Kaaks, Rudolf
AU - Gunter, Marc J.
AU - Viallon, Vivian
AU - Dossus, Laure
N1 - Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2021/1/1
Y1 - 2021/1/1
N2 - Background: Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity. endometrial cancer link in postmenopausal women. Methods: We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis. Results: The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5-<25 kg/m2 was 2.51 (95% confidence interval, 1.26-5.02). The ORsNIE were 1.95 (1.01-3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06-1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71-1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88-1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89-1.67) through estrogens beyond preceding biomarkers (21% PM). The ORNDE not through biomarkers was 1.29 (0.54-3.09). Waist circumference gave similar results. Conclusions: Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight. Impact: If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.
AB - Background: Adiposity increases endometrial cancer risk, possibly through inflammation, hyperinsulinemia, and increasing estrogens. We aimed to quantify the mediating effects of adiponectin (anti-inflammatory adipocytokine); IL6, IL1-receptor antagonist, TNF receptor 1 and 2, and C-reactive protein (inflammatory status biomarkers); C-peptide (hyperinsulinemia biomarker); and free estradiol and estrone (estrogen biomarkers) in the adiposity. endometrial cancer link in postmenopausal women. Methods: We used data from a case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC). Eligible women did not have cancer, hysterectomy, and diabetes; did not use oral contraceptives or hormone therapy; and were postmenopausal at recruitment. Mediating pathways from adiposity to endometrial cancer were investigated by estimating natural indirect (NIE) and direct (NDE) effects using sequential mediation analysis. Results: The study included 163 cases and 306 controls. The adjusted OR for endometrial cancer for body mass index (BMI) ≥30 versus ≥18.5-<25 kg/m2 was 2.51 (95% confidence interval, 1.26-5.02). The ORsNIE were 1.95 (1.01-3.74) through all biomarkers [72% proportion mediated (PM)] decomposed as: 1.35 (1.06-1.73) through pathways originating with adiponectin (33% PM); 1.13 (0.71-1.80) through inflammation beyond (the potential influence of) adiponectin (13% PM); 1.05 (0.88-1.24) through C-peptide beyond adiponectin and inflammation (5% PM); and 1.22 (0.89-1.67) through estrogens beyond preceding biomarkers (21% PM). The ORNDE not through biomarkers was 1.29 (0.54-3.09). Waist circumference gave similar results. Conclusions: Reduced adiponectin and increased inflammatory biomarkers, C-peptide, and estrogens mediated approximately 70% of increased odds of endometrial cancer in women with obesity versus normal weight. Impact: If replicated, these results could have implications for identifying targets for intervention to reduce endometrial cancer risk in women with obesity.
UR - http://www.scopus.com/inward/record.url?scp=85101034657&partnerID=8YFLogxK
U2 - 10.1158/1055-9965.EPI-20-0965
DO - 10.1158/1055-9965.EPI-20-0965
M3 - Article
C2 - 33008875
AN - SCOPUS:85101034657
SN - 1055-9965
VL - 30
SP - 104
EP - 113
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 1
ER -