Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort

Research output: Contribution to journalArticle


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 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.


  • Renée T Fortner
  • Allison F Vitonis
  • Helena Schock
  • Anika Hüsing
  • Theron Johnson
  • Raina N Fichorova
  • Titilayo Fashemi
  • Hidemi S Yamamoto
  • Anne Tjønneland
  • Louise Hansen
  • Kim Overvad
  • Marie-Christine Boutron-Ruault,
  • Marina Kvaskoff
  • Gianluca Severi
  • Heiner Boeing
  • Antonia Trichopoulou
  • Vassiliki Benetou
  • Carlo La Vecchia
  • Domenico Palli
  • Sabina Sieri
  • Rosario Tumino
  • Giuseppe Matullo
  • Amalia Mattiello
  • N Charlotte Onland-Moret
  • Petra H. Peeters
  • Elisabete Weiderpass
  • Inger Torhild Gram
  • Mie Jareid
  • J Ramón Quirós
  • Eric J Duell
  • Maria Jose Sánchez
  • María-Dolores Chirlaque
  • Eva Ardanaz
  • Nerea Larrañaga
  • Annika Idahl
  • Kay-Tee Khaw
  • Naomi Allen
  • Marc Gunter
  • Mattias Johansson
  • Laure Dossus
  • Melissa A Merritt
  • Elio Riboli
  • Daniel W Cramer
  • Rudolf Kaaks
  • Kathryn L Terry
External organisations
  • German Cancer Research Centre
  • Brigham and Women's Hospital / Harvard Medical School
  • Harvard Medical School
  • Danish Cancer Society Research Center
  • Aarhus University
  • Centre for Research in Epidemiology and Population Health (CESP)
  • University of Paris-Sud
  • Human Genetics Foundation (HuGeF)
  • German Institute of Human Nutrition
  • Hellenic Health Foundation, Athens
  • National and Kapodistrian University of Athens
  • University of Milan
  • Cancer Research and Prevention Institute (ISPO)
  • Istituto Nazionale dei Tumori
  • Azienda Sanitaria Provinciale di Ragusa
  • Citta' della Salute e della Scienza Hospital-University of Turin
  • University of Naples Federico II
  • University Medical Center Utrecht
  • Imperial College London
  • UiT The Arctic University of Norway, Tromsø
  • Cancer Registry of Norway Institute of Population-Based Cancer Research
  • Karolinska Institutet
  • Folkhälsan Research Center
  • Public Health Directorate
  • Catalan Institute of Oncology
  • Instituto de Investigación Biosanitaria de Granada (Granada.ibs)
  • CIBER Epidemiology and Public Health (CIBERESP)
  • Murcia Regional Health Authority
  • University of Murcia
  • Health Research Institute of Navarra (IDISNA)
  • Skåne University Hospital
  • Umeå University
  • University of Cambridge
  • University of Oxford
  • International Agency for Research on Cancer, World Health Organization
  • Utrecht University
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology


  • CA125, CA15.3, Early detection markers, HE4, Ovarian cancer
Original languageEnglish
Article number20
Pages (from-to)1-14
Number of pages14
JournalJournal of Ovarian Research
Issue number1
Publication statusPublished - 2017 Mar 20
Publication categoryResearch