@article{3108815,
    title = "Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort",
    author = "Fortner, R.T. and Vitonis, A.F. and Schock, H. and Hüsing, A. and Johnson, T. and Fichorova, R.N. and Fashemi, T. and Yamamoto, H.S. and Tjønneland, A. and Hansen, L. and Overvad, K. and Boutron-Ruault, M.-C. and Kvaskoff, M. and Severi, G. and Boeing, H. and Trichopoulou, A. and Benetou, V. and La Vecchia, C. and Palli, D. and Sieri, S. and Tumino, R. and Matullo, G. and Mattiello, A. and Onland-Moret, N.C. and Peeters, P.H. and Weiderpass, E. and Gram, I.T. and Jareid, M. and Quirós, J.R. and Duell, E.J. and Sánchez, M.-J. and Chirlaque, M.D. and Ardanaz, E. and Larrañaga, N. and Nodin, B. and Brändstedt, J. and Idahl, A. and Khaw, K.-T. and Allen, N. and Gunter, M. and Johansson, M. and Dossus, L. and Merritt, M.A. and Riboli, E. and Cramer, D.W. and Kaaks, R. and Terry, K.L.",
    journal = "Journal of Ovarian Research",
    year = "2017",
    volume = "10",
    number = "1",
    pages = "1-14",
    publisher = "BioMed Central Ltd.",
    issn = "1757-2215",
    doi = "10.1186/s13048-017-0315-6",
    keywords = "CA 125 antigen;  CA 15-3 antigen;  CA 72-4 antigen;  estrogen;  tumor marker, adult;  age;  aged;  Article;  blood sampling;  cancer hormone therapy;  case control study;  cohort analysis;  cross-sectional study;  early cancer diagnosis;  Europe;  female;  geometry;  human;  hysterectomy;  lifestyle;  major clinical study;  ovariectomy;  ovary cancer;  parity;  postmenopause;  prediction;  premenopause;  reproductive health;  smoking;  treatment duration;  area under the curve;  blood;  early cancer diagnosis;  health survey;  middle aged;  Ovarian Neoplasms;  risk factor, Adult;  Aged;  Area Under Curve;  Biomarkers, Tumor;  Case-Control Studies;  Cohort Studies;  Cross-Sectional Studies;  Early Detection of Cancer;  Europe;  Female;  Humans;  Middle Aged;  Ovarian Neoplasms;  Population Surveillance;  Risk Factors",
    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 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. © 2017 The Author(s)."
}