Adiposity and endometrial cancer risk in postmenopausal women: a sequential causal mediation analysis

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Adiposity and endometrial cancer risk in postmenopausal women : a sequential causal mediation analysis. / Dashti, S Ghazaleh; English, Dallas R; Simpson, Julie A; Karahalios, Amalia; Moreno-Betancur, Margarita; Biessy, Carine; Rinaldi, Sabina; Ferrari, Pietro; Tjonneland, Anne; Halkjær, Jytte; Dahm, Christina C; Vistisen, Helene Tilma; Menegaux, Florence; Perduca, Vittorio; Severi, Gianluca; Aleksandrova, Krasimira; Schulze, Matthias B; Masala, Giovanna; Sieri, Sabina; Tumino, Rosario; Macciotta, Alessandra; Panico, Salvatore; Hiensch, Anouk E; May, Anne M; Quirós, J Ramón; Agudo, Antonio; Sánchez, Maria-Jose; Amiano, Pilar; Colorado-Yohar, Sandra; Ardanaz, Eva; Allen, Naomi E; Weiderpass, Elisabete; Fortner, Renée Turzanski; Christakoudi, Sofia; Tsilidis, Konstantinos K; Riboli, Elio; Kaaks, Rudolf; Gunter, Marc J; Viallon, Vivian; Dossus, Laure.

In: Cancer Epidemiology, Biomarkers & Prevention, Vol. 30, No. 1, 01.2021, p. 104-113.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Dashti, SG, English, DR, Simpson, JA, Karahalios, A, Moreno-Betancur, M, Biessy, C, Rinaldi, S, Ferrari, P, Tjonneland, A, Halkjær, J, Dahm, CC, Vistisen, HT, Menegaux, F, Perduca, V, Severi, G, Aleksandrova, K, Schulze, MB, Masala, G, Sieri, S, Tumino, R, Macciotta, A, Panico, S, Hiensch, AE, May, AM, Quirós, JR, Agudo, A, Sánchez, M-J, Amiano, P, Colorado-Yohar, S, Ardanaz, E, Allen, NE, Weiderpass, E, Fortner, RT, Christakoudi, S, Tsilidis, KK, Riboli, E, Kaaks, R, Gunter, MJ, Viallon, V & Dossus, L 2021, 'Adiposity and endometrial cancer risk in postmenopausal women: a sequential causal mediation analysis', Cancer Epidemiology, Biomarkers & Prevention, vol. 30, no. 1, pp. 104-113. https://doi.org/10.1158/1055-9965.EPI-20-0965

APA

Dashti, S. G., English, D. R., Simpson, J. A., Karahalios, A., Moreno-Betancur, M., Biessy, C., Rinaldi, S., Ferrari, P., Tjonneland, A., Halkjær, J., Dahm, C. C., Vistisen, H. T., Menegaux, F., Perduca, V., Severi, G., Aleksandrova, K., Schulze, M. B., Masala, G., Sieri, S., ... Dossus, L. (2021). Adiposity and endometrial cancer risk in postmenopausal women: a sequential causal mediation analysis. Cancer Epidemiology, Biomarkers & Prevention, 30(1), 104-113. https://doi.org/10.1158/1055-9965.EPI-20-0965

CBE

Dashti SG, English DR, Simpson JA, Karahalios A, Moreno-Betancur M, Biessy C, Rinaldi S, Ferrari P, Tjonneland A, Halkjær J, Dahm CC, Vistisen HT, Menegaux F, Perduca V, Severi G, Aleksandrova K, Schulze MB, Masala G, Sieri S, Tumino R, Macciotta A, Panico S, Hiensch AE, May AM, Quirós JR, Agudo A, Sánchez M-J, Amiano P, Colorado-Yohar S, Ardanaz E, Allen NE, Weiderpass E, Fortner RT, Christakoudi S, Tsilidis KK, Riboli E, Kaaks R, Gunter MJ, Viallon V, Dossus L. 2021. Adiposity and endometrial cancer risk in postmenopausal women: a sequential causal mediation analysis. Cancer Epidemiology, Biomarkers & Prevention. 30(1):104-113. https://doi.org/10.1158/1055-9965.EPI-20-0965

MLA

Vancouver

Dashti SG, English DR, Simpson JA, Karahalios A, Moreno-Betancur M, Biessy C et al. Adiposity and endometrial cancer risk in postmenopausal women: a sequential causal mediation analysis. Cancer Epidemiology, Biomarkers & Prevention. 2021 Jan;30(1):104-113. https://doi.org/10.1158/1055-9965.EPI-20-0965

Author

Dashti, S Ghazaleh ; English, Dallas R ; Simpson, Julie A ; Karahalios, Amalia ; Moreno-Betancur, Margarita ; Biessy, Carine ; Rinaldi, Sabina ; Ferrari, Pietro ; Tjonneland, Anne ; Halkjær, Jytte ; Dahm, Christina C ; Vistisen, Helene Tilma ; Menegaux, Florence ; Perduca, Vittorio ; Severi, Gianluca ; Aleksandrova, Krasimira ; Schulze, Matthias B ; Masala, Giovanna ; Sieri, Sabina ; Tumino, Rosario ; Macciotta, Alessandra ; Panico, Salvatore ; Hiensch, Anouk E ; May, Anne M ; Quirós, J Ramón ; Agudo, Antonio ; Sánchez, Maria-Jose ; Amiano, Pilar ; Colorado-Yohar, Sandra ; Ardanaz, Eva ; Allen, Naomi E ; Weiderpass, Elisabete ; Fortner, Renée Turzanski ; Christakoudi, Sofia ; Tsilidis, Konstantinos K ; Riboli, Elio ; Kaaks, Rudolf ; Gunter, Marc J ; Viallon, Vivian ; Dossus, Laure. / Adiposity and endometrial cancer risk in postmenopausal women : a sequential causal mediation analysis. In: Cancer Epidemiology, Biomarkers & Prevention. 2021 ; Vol. 30, No. 1. pp. 104-113.

Bibtex

@article{c349f32f8eb54c48a76e215e843785c4,
title = "Adiposity and endometrial cancer risk in postmenopausal women: a sequential causal mediation analysis",
abstract = "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.",
author = "Dashti, {S Ghazaleh} and English, {Dallas R} and Simpson, {Julie A} and Amalia Karahalios and Margarita Moreno-Betancur and Carine Biessy and Sabina Rinaldi and Pietro Ferrari and Anne Tjonneland and Jytte Halkj{\ae}r and Dahm, {Christina C} and Vistisen, {Helene Tilma} and Florence Menegaux and Vittorio Perduca and Gianluca Severi and Krasimira Aleksandrova and Schulze, {Matthias B} and Giovanna Masala and Sabina Sieri and Rosario Tumino and Alessandra Macciotta and Salvatore Panico and Hiensch, {Anouk E} and May, {Anne M} and Quir{\'o}s, {J Ram{\'o}n} and Antonio Agudo and Maria-Jose S{\'a}nchez and Pilar Amiano and Sandra Colorado-Yohar and Eva Ardanaz and Allen, {Naomi E} and Elisabete Weiderpass and Fortner, {Ren{\'e}e Turzanski} and Sofia Christakoudi and Tsilidis, {Konstantinos K} and Elio Riboli and Rudolf Kaaks and Gunter, {Marc J} and Vivian Viallon and Laure Dossus",
note = "Copyright {\textcopyright}2020, American Association for Cancer Research.",
year = "2021",
month = jan,
doi = "10.1158/1055-9965.EPI-20-0965",
language = "English",
volume = "30",
pages = "104--113",
journal = "Cancer Epidemiology, Biomarkers & Prevention",
issn = "1055-9965",
publisher = "American Association for Cancer Research (A A C R)",
number = "1",

}

RIS

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 -