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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

Fortner, Renée T ; Vitonis, Allison F ; Schock, Helena ; Hüsing, Anika ; Johnson, Theron ; Fichorova, Raina N ; Fashemi, Titilayo ; Yamamoto, Hidemi S ; Tjønneland, Anne and Hansen, Louise , et al. (2017) In Journal of Ovarian Research 10(1). p.1-14
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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
CA125, CA15.3, Early detection markers, HE4, Ovarian cancer
in
Journal of Ovarian Research
volume
10
issue
1
article number
20
pages
14 pages
publisher
BioMed Central (BMC)
external identifiers
  • scopus:85015771545
  • pmid:28320479
  • pmid:28320479
  • wos:000396771200001
ISSN
1757-2215
DOI
10.1186/s13048-017-0315-6
language
English
LU publication?
yes
id
14139206-cc32-4c82-a679-36e8ada53b80
date added to LUP
2017-04-23 14:08:15
date last changed
2025-01-07 11:54:23
@article{14139206-cc32-4c82-a679-36e8ada53b80,
  abstract     = {{<p>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 &lt; 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.</p>}},
  author       = {{Fortner, Renée T and Vitonis, Allison F and Schock, Helena and Hüsing, Anika and Johnson, Theron and Fichorova, Raina N and Fashemi, Titilayo and Yamamoto, Hidemi S and Tjønneland, Anne and Hansen, Louise and Overvad, Kim and Boutron-Ruault,, Marie-Christine and Kvaskoff, Marina and Severi, Gianluca and Boeing, Heiner and Trichopoulou, Antonia and Benetou, Vassiliki and Vecchia, Carlo La and Palli, Domenico and Sieri, Sabina and Tumino, Rosario and Matullo, Giuseppe and Mattiello, Amalia and Onland-Moret, N Charlotte and Peeters, Petra H. and Weiderpass, Elisabete and Gram, Inger Torhild and Jareid, Mie and Quirós, J Ramón and Duell, Eric J and Sánchez, Maria Jose and Chirlaque, María-Dolores and Ardanaz, Eva and Larrañaga, Nerea and Nodin, Björn and Brändstedt, Jenny and Idahl, Annika and Khaw, Kay-Tee and Allen, Naomi and Gunter, Marc and Johansson, Mattias and Dossus, Laure and Merritt, Melissa A and Riboli, Elio and Cramer, Daniel W and Kaaks, Rudolf and Terry, Kathryn L}},
  issn         = {{1757-2215}},
  keywords     = {{CA125; CA15.3; Early detection markers; HE4; Ovarian cancer}},
  language     = {{eng}},
  month        = {{03}},
  number       = {{1}},
  pages        = {{1--14}},
  publisher    = {{BioMed Central (BMC)}},
  series       = {{Journal of Ovarian Research}},
  title        = {{Correlates of circulating ovarian cancer early detection markers and their contribution to discrimination of early detection models : results from the EPIC cohort}},
  url          = {{http://dx.doi.org/10.1186/s13048-017-0315-6}},
  doi          = {{10.1186/s13048-017-0315-6}},
  volume       = {{10}},
  year         = {{2017}},
}