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

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Title: Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models: results from the EPIC cohort.
Authors: Fortner, RT
Vitonis, AF
Schock, H
Hüsing, A
Johnson, T
Fichorova, RN
Fashemi, T
Yamamoto, HS
Tjønneland, A
Hansen, L
Overvad, K
Boutron-Ruault, MC
Kvaskoff, M
Severi, G
Boeing, H
Trichopoulou, A
Benetou, V
La Vecchia, C
Palli, D
Sieri, S
Tumino, R
Matullo, G
Mattiello, A
Onland-Moret, NC
Peeters, PH
Weiderpass, E
Gram, IT
Jareid, M
Quirós, JR
Duell, EJ
Sánchez, MJ
Chirlaque, MD
Ardanaz, E
Larrañaga, N
Nodin, B
Brändstedt, J
Idahl, A
Khaw, KT
Allen, N
Gunter, M
Johansson, M
Dossus, L
Merritt, MA
Riboli, E
Cramer, DW
Kaaks, R
Terry, KL
Item Type: Journal 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 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.
Issue Date: 20-Mar-2017
Date of Acceptance: 8-Mar-2017
URI: http://hdl.handle.net/10044/1/45522
DOI: 10.1186/s13048-017-0315-6
ISSN: 1757-2215
Publisher: BioMed Central
Start Page: 20
End Page: 20
Journal / Book Title: Journal of Ovarian Research
Volume: 10
Issue: 1
Keywords: Science & Technology
Life Sciences & Biomedicine
Reproductive Biology
Ovarian cancer
Early detection markers
CA125
CA15.3
HE4
HEALTHY POSTMENOPAUSAL WOMEN
EPIDIDYMIS PROTEIN 4
HORMONE REPLACEMENT THERAPY
TUMOR-MARKER
SERUM CA125
MENSTRUAL-CYCLE
ANTIGEN 125
HIGH-RISK
NORMAL-PREGNANCY
CA-125
CA125
CA15.3
Early detection markers
HE4
Ovarian cancer
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
Humans
Ovarian Neoplasms
Population Surveillance
Area Under Curve
Risk Factors
Case-Control Studies
Cohort Studies
Cross-Sectional Studies
Adult
Aged
Middle Aged
Europe
Female
Early Detection of Cancer
Biomarkers, Tumor
Publication Status: Published
Conference Place: England
Appears in Collections:Epidemiology, Public Health and Primary Care



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