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 Tjønneland; Agnès Fournier; Francesca Romana Mancini; Marina Kvaskoff; Heiner Boeing; Antonia Trichopoulou; Anna Karakatsani; Elissavet Valanou; Claudia Agnoli; Carlotta Sacerdote; Giovanna Masala; Amalia Mattiello; Rosario Tumino; Carla H. Van Gils; Guri Skeie; Inger Torhild Gram; Elisabete Weiderpass; Leila Lujan-Barroso; Dafina Petrova; Carmen Santiuste; J. Ramón Quirós; Aurelio Barricarte; Pilar Amiano; Ruth C. Travis; Marc Gunter; Laure Dossus; Sofia Christakoudi; Rudolf Kaaks; Renée Turzanski 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 Tjønneland, Agnès Fournier, Francesca Romana Mancini, Marina Kvaskoff, Heiner Boeing, Antonia Trichopoulou, Anna Karakatsani, Elissavet Valanou, Claudia Agnoli, Carlotta Sacerdote, Giovanna Masala, Amalia Mattiello, Rosario Tumino, Carla H. Van GilsGuri Skeie, Inger Torhild Gram, Elisabete Weiderpass, Leila Lujan-Barroso, Dafina Petrova, Carmen Santiuste, J. Ramón Quirós, Aurelio Barricarte, Pilar Amiano, Ruth C. Travis, Marc Gunter, Laure Dossus, Sofia Christakoudi, Rudolf Kaaks, Renée Turzanski Fortner

Section of Environmental Health

4 Citations (Scopus)

Abstract

Background: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor kB (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
Journal	Cancer Epidemiology, Biomarkers & Prevention
Volume	28
Issue number	10
Pages (from-to)	1746-1754
Number of pages	9
ISSN	1055-9965
DOIs	https://doi.org/10.1158/1055-9965.epi-19-0241
Publication status	Published - 2019

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Sarink, D., Yang, J., Johnson, T., Chang-Claude, J., Overvad, K., Olsen, A., Tjønneland, A., Fournier, A., Mancini, F. R., Kvaskoff, M., Boeing, H., Trichopoulou, A., Karakatsani, A., Valanou, E., Agnoli, C., Sacerdote, C., Masala, G., Mattiello, A., Tumino, 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

Sarink, D, Yang, J, Johnson, T, Chang-Claude, J, Overvad, K, Olsen, A, Tjønneland, A, Fournier, A, Mancini, FR, Kvaskoff, M, Boeing, H, Trichopoulou, A, Karakatsani, A, Valanou, E, Agnoli, C, Sacerdote, C, Masala, G, Mattiello, A, Tumino, R, Van Gils, CH, Skeie, G, Gram, IT, Weiderpass, E, Lujan-Barroso, L, Petrova, D, Santiuste, C, Ramón Quirós, J, Barricarte, A, Amiano, P, Travis, RC, Gunter, M, 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

@article{3b22f4df9cfd4eccaa0d5c3455b31437,

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 kB (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 (Ptrend < 0.03) and higher OPG concentrations in all women (Ptrend < 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG (Ptrend < 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 (Ptrend < 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 Tj{\o}nneland and Agn{\`e}s Fournier and Mancini, {Francesca Romana} and Marina Kvaskoff 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 Tumino and {Van Gils}, {Carla H.} and Guri Skeie and Gram, {Inger Torhild} and Elisabete Weiderpass and Leila Lujan-Barroso and Dafina Petrova and Carmen Santiuste and {Ram{\'o}n Quir{\'o}s}, J. and Aurelio Barricarte and Pilar Amiano and Travis, {Ruth C.} and Marc Gunter and Laure Dossus and Sofia Christakoudi and Rudolf Kaaks and Fortner, {Ren{\'e}e Turzanski}",

year = "2019",

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 (A A C R)",

number = "10",

}

TY - JOUR

T1 - Reproductive and Lifestyle Factors and Circulating sRANKL and OPG Concentrations in Women: 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 - Tjønneland, Anne

AU - Fournier, Agnès

AU - Mancini, Francesca Romana

AU - Kvaskoff, Marina

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 - Tumino, Rosario

AU - Van Gils, Carla H.

AU - Skeie, Guri

AU - Gram, Inger Torhild

AU - Weiderpass, Elisabete

AU - Lujan-Barroso, Leila

AU - Petrova, Dafina

AU - Santiuste, Carmen

AU - Ramón Quirós, J.

AU - Barricarte, Aurelio

AU - Amiano, Pilar

AU - Travis, Ruth C.

AU - Gunter, Marc

AU - Dossus, Laure

AU - Christakoudi, Sofia

AU - Kaaks, Rudolf

AU - Fortner, Renée Turzanski

PY - 2019

Y1 - 2019

N2 - Background: Except for a documented increase in osteoprotegerin (OPG) concentrations with older age, data on determinants of soluble Receptor Activator of Nuclear Factor kB (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 (Ptrend < 0.03) and higher OPG concentrations in all women (Ptrend < 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG (Ptrend < 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 (Ptrend < 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 kB (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 (Ptrend < 0.03) and higher OPG concentrations in all women (Ptrend < 0.01). Longer duration of oral contraceptive use among premenopausal women and postmenopausal PMH users was associated with higher OPG (Ptrend < 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 (Ptrend < 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.

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

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

M3 - Journal 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

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