Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort
Fortner, Renée T.; Vitonis, Allison F.; Schock, Helena; Hüsing, Anika; Johnson, Theron; Fichorova, Raina N.; Fashemi, Titilayo; Yamamoto, Hidemi S.; Tjønneland, Anne; Hansen, Louise; Overvad, Kim; Boutron-Ruault, Marie Christine; Kvaskoff, Marina; Severi, Gianluca; Boeing, Heiner; Trichopoulou, Antonia; Benetou, Vassiliki; La Vecchia, Carlo; Palli, Domenico; Sieri, Sabina; Tumino, Rosario; Matullo, Giuseppe; Mattiello, Amalia; Onland-Moret, N. Charlotte; Peeters, Petra H.; Weiderpass, Elisabete; Gram, Inger Torhild; Jareid, Mie; Quirós, J. Ramón; Duell, Eric J.; Sánchez, Maria Jose; Chirlaque, María Dolores; Ardanaz, Eva; Larrañaga, Nerea; Nodin, Björn; Brändstedt, Jenny; Idahl, Annika; Khaw, Kay Tee; Allen, Naomi; Gunter, Marc; Johansson, Mattias; Dossus, Laure; Merritt, Melissa A.; Riboli, Elio; Cramer, Daniel W.; Kaaks, Rudolf; Terry, Kathryn L.
(2017) Journal of Ovarian Research, volume 10, issue 1
(Article)
Abstract
Background: Ovarian cancer early detection markers CA125, CA15.3, HE4, and CA72.4 vary between healthy women, limiting their utility for screening. Methods: We evaluated cross-sectional relationships between lifestyle and reproductive factors and these markers among controls (n = 1910) from a nested case-control study in the European Prospective Investigation into Cancer
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and Nutrition (EPIC). Improvements in discrimination of prediction models adjusting for correlates of the markers were evaluated among postmenopausal women in the nested case-control study (n = 590 cases). Generalized linear models were used to calculate geometric means of CA125, CA15.3, and HE4. CA72.4 above vs. below limit of detection was evaluated using logistic regression. Early detection prediction was modeled using conditional logistic regression. Results: CA125 concentrations were lower, and CA15.3 higher, in post- vs. premenopausal women (p ≤ 0.02). Among postmenopausal women, CA125 was higher among women with higher parity and older age at menopause (ptrend ≤ 0.02), but lower among women reporting oophorectomy, hysterectomy, ever use of estrogen-only hormone therapy, or current smoking (p <0.01). CA15.3 concentrations were higher among heavier women and in former smokers (p ≤ 0.03). HE4 was higher with older age at blood collection and in current smokers, and inversely associated with OC use duration, parity, and older age at menopause (≤ 0.02). No associations were observed with CA72.4. Adjusting for correlates of the markers in prediction models did not improve the discrimination. Conclusions: This study provides insights into sources of variation in ovarian cancer early detection markers in healthy women and informs about the utility of individualizing marker cutpoints based on epidemiologic factors.
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Keywords: CA125, CA15.3, Early detection markers, HE4, Ovarian cancer, Oncology, Obstetrics and Gynaecology, Journal Article
ISSN: 1757-2215
Publisher: BioMed Central
Note: Funding Information: This project was approved by the International Agency for Research on Cancer (IARC) Ethics Committee (Project No. 11-01) and the University of Heidelberg Ethics Commission (Project No. S542/2012). Since the identity of subjects providing specimens was anonymous to Brigham and Women’s Hospital (BWH) investigators, the research was declared exempt at BWH. The EPIC study protocol was approved by the ethical committees of IARC and the participating centers. All participants provided informed consent. Funding Information: This study was funded by the United States National Cancer Institute grant R01 CA 158119. 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), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy and National 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: © 2017 The Author(s).
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