RT Journal Article
SR Electronic
T1 Adiposity and Endometrial Cancer Risk in Postmenopausal Women: A Sequential Causal Mediation Analysis
JF Cancer Epidemiology Biomarkers & Prevention
JO Cancer Epidemiol Biomarkers Prev
FD American Association for Cancer Research
DO 10.1158/1055-9965.EPI-20-0965
A1 Dashti, S. Ghazaleh
A1 English, Dallas R.
A1 Simpson, Julie A.
A1 Karahalios, Amalia
A1 Moreno-Betancur, Margarita
A1 Biessy, Carine
A1 Rinaldi, Sabina
A1 Ferrari, Pietro
A1 Tjønneland, Anne
A1 Halkjær, Jytte
A1 Dahm, Christina C.
A1 Vistisen, Helene Tilma
A1 Menegaux, Florence
A1 Perduca, Vittorio
A1 Severi, Gianluca
A1 Aleksandrova, Krasimira
A1 Schulze, Matthias B.
A1 Masala, Giovanna
A1 Sieri, Sabina
A1 Tumino, Rosario
A1 Macciotta, Alessandra
A1 Panico, Salvatore
A1 Hiensch, Anouk E.
A1 May, Anne M.
A1 Quirós, J. Ramón
A1 Agudo, Antonio
A1 Sánchez, Maria-Jose
A1 Amiano, Pilar
A1 Colorado-Yohar, Sandra
A1 Ardanaz, Eva
A1 Allen, Naomi E.
A1 Weiderpass, Elisabete
A1 Fortner, Renée Turzanski
A1 Christakoudi, Sofia
A1 Tsilidis, Konstantinos K.
A1 Riboli, Elio
A1 Kaaks, Rudolf
A1 Gunter, Marc J.
A1 Viallon, Vivian
A1 Dossus, Laure
YR 2020
UL http://cebp.aacrjournals.org/content/early/2020/11/03/1055-9965.EPI-20-0965.abstract
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.