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 - Tjonneland, 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 - Copyright ©2020, American Association for Cancer Research.

PY - 2021/1

Y1 - 2021/1

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.

U2 - 10.1158/1055-9965.EPI-20-0965

DO - 10.1158/1055-9965.EPI-20-0965

M3 - Journal article

C2 - 33008875

VL - 30

SP - 104

EP - 113

JO - Cancer Epidemiology, Biomarkers & Prevention

JF - Cancer Epidemiology, Biomarkers & Prevention

SN - 1055-9965

IS - 1

ER -