Reproductive and lifestyle factors and circulating sRANKL and OPG concentrations in women: Results from the EPIC cohort

Danja Sarink; Jiaxi Yang; Theron Johnson; Jenny Chang-Claude; Kim Overvad; Anja Olsen; Anne Tjonneland; Agnes Fournier; Marina Kvaskoff; Francesca Romana Mancini; Heiner Boeing; Antonia Trichopoulou; Anna Karakatsani; Elissavet Valanou; Claudia Agnoli; Carlotta Sacerdote; Giovanna Masala; Amalia Mattiello; Rosario Tunino; Carla H van Gils; Guri Skeie; Inger T Gram; Elisabete Weiderpass; Leila Lujan-Barroso; Dafina Petrova; Carmen Santiuste; J Ramón Quirós; Aurelio Barricarte; Pilar Amiano; Ruth C Travis; Marc J Gunter; Laure Dossus; Sofia Christakoudi; Rudolf Kaaks; Renée T Fortner

doi:10.1158/1055-9965.EPI-19-0241

Reproductive and lifestyle factors and circulating sRANKL and OPG concentrations in women: Results from the EPIC cohort

Danja Sarink, Jiaxi Yang, Theron Johnson, Jenny Chang-Claude, Kim Overvad, Anja Olsen, Anne Tjonneland, Agnes Fournier, Marina Kvaskoff, Francesca Romana Mancini, Heiner Boeing, Antonia Trichopoulou, Anna Karakatsani, Elissavet Valanou, Claudia Agnoli, Carlotta Sacerdote, Giovanna Masala, Amalia Mattiello, Rosario Tunino, Carla H van GilsGuri Skeie, Inger T Gram, Elisabete Weiderpass, Leila Lujan-Barroso, Dafina Petrova, Carmen Santiuste, J Ramón Quirós, Aurelio Barricarte, Pilar Amiano, Ruth C Travis, Marc J Gunter, Laure Dossus, Sofia Christakoudi, Rudolf Kaaks, Renée T Fortner

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women.

METHODS: This study includes 2,016 controls [ n = 1,552 (76%) postmenopausal, n = 757 (38%) using postmenopausal hormone therapy (PMH)] from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an ELISA and serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors.

RESULTS: Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women ( P trend ≤ 0.03) and higher OPG concentrations in all women ( P trend ≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG ( P trend ≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking ( P ≤ 0.01). sRANKL concentrations were higher among women with higher BMI ( P trend ≤ 0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations.

CONCLUSIONS: Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women.

IMPACT: This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.

Original language	English
Pages (from-to)	1746-1754
Number of pages	9
Journal	Cancer Epidemiology Biomarkers & Prevention
Volume	28
Issue number	10
Early online date	10 Jul 2019
DOIs	https://doi.org/10.1158/1055-9965.EPI-19-0241
Publication status	Published - Oct 2019

Access to Document

10.1158/1055-9965.EPI-19-0241

Cite this

Sarink, D., Yang, J., Johnson, T., Chang-Claude, J., Overvad, K., Olsen, A., Tjonneland, A., Fournier, A., Kvaskoff, M., Romana Mancini, F., Boeing, H., Trichopoulou, A., Karakatsani, A., Valanou, E., Agnoli, C., Sacerdote, C., Masala, G., Mattiello, A., Tunino, R., ... Fortner, R. T. (2019). Reproductive and lifestyle factors and circulating sRANKL and OPG concentrations in women: Results from the EPIC cohort. Cancer Epidemiology Biomarkers & Prevention, 28(10), 1746-1754. https://doi.org/10.1158/1055-9965.EPI-19-0241

@article{1ba7eeb068894b5ca0565959805e440b,

title = "Reproductive and lifestyle factors and circulating sRANKL and OPG concentrations in women: Results from the EPIC cohort",

abstract = "BACKGROUND: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women.METHODS: This study includes 2,016 controls [ n = 1,552 (76\%) postmenopausal, n = 757 (38\%) using postmenopausal hormone therapy (PMH)] from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an ELISA and serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors. RESULTS: Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women ( P trend ≤ 0.03) and higher OPG concentrations in all women ( P trend ≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG ( P trend ≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking ( P ≤ 0.01). sRANKL concentrations were higher among women with higher BMI ( P trend ≤ 0.01). The evaluated factors accounted for 12\% of the variation in sRANKL concentrations and 21\% of the variation in OPG concentrations. CONCLUSIONS: Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women.IMPACT: This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.",

author = "Danja Sarink and Jiaxi Yang and Theron Johnson and Jenny Chang-Claude and Kim Overvad and Anja Olsen and Anne Tjonneland and Agnes Fournier and Marina Kvaskoff and \{Romana Mancini\}, Francesca and Heiner Boeing and Antonia Trichopoulou and Anna Karakatsani and Elissavet Valanou and Claudia Agnoli and Carlotta Sacerdote and Giovanna Masala and Amalia Mattiello and Rosario Tunino and \{van Gils\}, \{Carla H\} and Guri Skeie and Gram, \{Inger T\} and Elisabete Weiderpass and Leila Lujan-Barroso and Dafina Petrova and Carmen Santiuste and Quir{\'o}s, \{J Ram{\'o}n\} and Aurelio Barricarte and Pilar Amiano and Travis, \{Ruth C\} and Gunter, \{Marc J\} and Laure Dossus and Sofia Christakoudi and Rudolf Kaaks and Fortner, \{Ren{\'e}e T\}",

note = "Funding Information: This project was funded by research grant \#111454 from the Deutsche Kresbshilfe. R.T. Fortner was supported by aMarie Curie International Incoming Fellowship of the European Commission's Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle G{\'e}n{\'e}rale de l'Education Nationale, Institut National de la Sant{\'e} et de la Recherche M{\'e}dicale (INSERM; France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy andNational Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; PI13/01162 to EPIC-Murcia, Regional Governments of Andaluc{\'i}a, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Sk{\aa}ne and V{\"a}sterbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford; United Kingdom). Publisher Copyright: {\textcopyright} 2019 American Association for Cancer Research.",

year = "2019",

month = oct,

doi = "10.1158/1055-9965.EPI-19-0241",

language = "English",

volume = "28",

pages = "1746--1754",

journal = "Cancer Epidemiology Biomarkers \& Prevention",

issn = "1055-9965",

publisher = "American Association for Cancer Research Inc.",

number = "10",

}

Sarink, D, Yang, J, Johnson, T, Chang-Claude, J, Overvad, K, Olsen, A, Tjonneland, A, Fournier, A, Kvaskoff, M, Romana Mancini, F, Boeing, H, Trichopoulou, A, Karakatsani, A, Valanou, E, Agnoli, C, Sacerdote, C, Masala, G, Mattiello, A, Tunino, R, van Gils, CH, Skeie, G, Gram, IT, Weiderpass, E, Lujan-Barroso, L, Petrova, D, Santiuste, C, Quirós, JR, Barricarte, A, Amiano, P, Travis, RC, Gunter, MJ, Dossus, L, Christakoudi, S, Kaaks, R & Fortner, RT 2019, 'Reproductive and lifestyle factors and circulating sRANKL and OPG concentrations in women: Results from the EPIC cohort', Cancer Epidemiology Biomarkers & Prevention, vol. 28, no. 10, pp. 1746-1754. https://doi.org/10.1158/1055-9965.EPI-19-0241

TY - JOUR

T1 - Reproductive and lifestyle factors and circulating sRANKL and OPG concentrations in women

T2 - Results from the EPIC cohort

AU - Sarink, Danja

AU - Yang, Jiaxi

AU - Johnson, Theron

AU - Chang-Claude, Jenny

AU - Overvad, Kim

AU - Olsen, Anja

AU - Tjonneland, Anne

AU - Fournier, Agnes

AU - Kvaskoff, Marina

AU - Romana Mancini, Francesca

AU - Boeing, Heiner

AU - Trichopoulou, Antonia

AU - Karakatsani, Anna

AU - Valanou, Elissavet

AU - Agnoli, Claudia

AU - Sacerdote, Carlotta

AU - Masala, Giovanna

AU - Mattiello, Amalia

AU - Tunino, Rosario

AU - van Gils, Carla H

AU - Skeie, Guri

AU - Gram, Inger T

AU - Weiderpass, Elisabete

AU - Lujan-Barroso, Leila

AU - Petrova, Dafina

AU - Santiuste, Carmen

AU - Quirós, J Ramón

AU - Barricarte, Aurelio

AU - Amiano, Pilar

AU - Travis, Ruth C

AU - Gunter, Marc J

AU - Dossus, Laure

AU - Christakoudi, Sofia

AU - Kaaks, Rudolf

AU - Fortner, Renée T

N1 - Funding Information: This project was funded by research grant #111454 from the Deutsche Kresbshilfe. R.T. Fortner was supported by aMarie Curie International Incoming Fellowship of the European Commission's Seventh Framework Programme (MC-IIF-623984). The coordination of EPIC is financially supported by the European Commission (DG-SANCO) and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM; France); German Cancer Aid, German Cancer Research Center (DKFZ), Federal Ministry of Education and Research (BMBF); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy andNational Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (the Netherlands); ERC-2009-AdG 232997 and Nordforsk, Nordic Centre of Excellence programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS), PI13/00061 to Granada; PI13/01162 to EPIC-Murcia, Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 and C8221/A19170 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk, MR/ M012190/1 to EPIC-Oxford; United Kingdom). Publisher Copyright: © 2019 American Association for Cancer Research.

PY - 2019/10

Y1 - 2019/10

N2 - BACKGROUND: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women.METHODS: This study includes 2,016 controls [ n = 1,552 (76%) postmenopausal, n = 757 (38%) using postmenopausal hormone therapy (PMH)] from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an ELISA and serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors. RESULTS: Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women ( P trend ≤ 0.03) and higher OPG concentrations in all women ( P trend ≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG ( P trend ≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking ( P ≤ 0.01). sRANKL concentrations were higher among women with higher BMI ( P trend ≤ 0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations. CONCLUSIONS: Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women.IMPACT: This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.

AB - BACKGROUND: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor κB (sRANKL) and OPG concentrations in women are limited. We evaluated reproductive and lifestyle factors as potential sources of variation in circulating sRANKL and OPG concentrations in pre- and postmenopausal women.METHODS: This study includes 2,016 controls [ n = 1,552 (76%) postmenopausal, n = 757 (38%) using postmenopausal hormone therapy (PMH)] from a breast cancer case-control study nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Serum sRANKL was measured using an ELISA and serum OPG using an electrochemiluminescent assay. Generalized linear models were used to evaluate associations between these analytes and reproductive and lifestyle factors. RESULTS: Older age at blood collection was associated with lower sRANKL concentrations in postmenopausal women ( P trend ≤ 0.03) and higher OPG concentrations in all women ( P trend ≤ 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG ( P trend ≤ 0.04). In postmenopausal non-PMH users, sRANKL concentrations were lower with longer duration of oral contraceptive use and current (vs. never) smoking ( P ≤ 0.01). sRANKL concentrations were higher among women with higher BMI ( P trend ≤ 0.01). The evaluated factors accounted for 12% of the variation in sRANKL concentrations and 21% of the variation in OPG concentrations. CONCLUSIONS: Circulating sRANKL and OPG concentrations are minimally impacted by hormone-related factors in pre- and postmenopausal women.IMPACT: This study suggests circulating concentrations of sRANKL and OPG are unlikely to be strongly modified by hormone-related reproductive and lifestyle factors.

UR - https://www.scopus.com/pages/publications/85072849223

U2 - 10.1158/1055-9965.EPI-19-0241

DO - 10.1158/1055-9965.EPI-19-0241

M3 - Article

C2 - 31292137

SN - 1055-9965

VL - 28

SP - 1746

EP - 1754

JO - Cancer Epidemiology Biomarkers & Prevention

JF - Cancer Epidemiology Biomarkers & Prevention

IS - 10

ER -

Reproductive and lifestyle factors and circulating sRANKL and OPG concentrations in women: Results from the EPIC cohort

Abstract

Access to Document

Other files and links

Fingerprint

Cite this