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Cancer Causes & Control

, Volume 28, Issue 5, pp 459–468 | Cite as

Predictors of pretreatment CA125 at ovarian cancer diagnosis: a pooled analysis in the Ovarian Cancer Association Consortium

  • Ana Babic
  • Daniel W. Cramer
  • Linda E. Kelemen
  • Martin Köbel
  • Helen Steed
  • Penelope M. Webb
  • Sharon E. Johnatty
  • Anna deFazio
  • Diether Lambrechts
  • Marc T. Goodman
  • Florian Heitz
  • Keitaro Matsuo
  • Satoyo Hosono
  • Beth Y. Karlan
  • Allan Jensen
  • Susanne K. Kjær
  • Ellen L. Goode
  • Tanja Pejovic
  • Melissa Moffitt
  • Estrid Høgdall
  • Claus Høgdall
  • Iain McNeish
  • Kathryn L. TerryEmail author
Original paper

Abstract

Purpose

Cancer antigen 125 (CA125) is a glycoprotein expressed by epithelial cells of several normal tissue types and overexpressed by several epithelial cancers. Serum CA125 levels are mostly used as an aid in the diagnosis of ovarian cancer patients, to monitor response to treatment and detect cancer recurrence. Besides tumor characteristics, CA125 levels are also influenced by several epidemiologic factors, such as age, parity, and oral contraceptive use. Identifying factors that influence CA125 levels in ovarian cancer patients could aid in the interpretation of CA125 values for individuals.

Methods

We evaluated predictors of pretreatment CA125 in 13 studies participating in the Ovarian Cancer Association Consortium. This analysis included a total of 5,091 women with invasive epithelial ovarian cancer with pretreatment CA125 measurements. We used probit scores to account for variability in CA125 between studies and linear regression to estimate the association between epidemiologic factors and tumor characteristics and pretreatment CA125 levels.

Results

In age-adjusted models, older age, history of pregnancy, history of tubal ligation, family history of breast cancer, and family history of ovarian cancer were associated with higher CA125 levels while endometriosis was associated with lower CA125 levels. After adjusting for tumor-related characteristics (stage, histology, grade), body mass index (BMI) higher than 30 kg/m2 was associated with 10% (95% CI 2, 19%) higher CA125 levels, while race (non-white vs. white) was associated with 15% (95% CI 4, 27%) higher CA125 levels.

Conclusion

Our results suggest that high BMI and race may influence CA125 levels independent of tumor characteristics. Validation is needed in studies that use a single assay for CA125 measurement and have a diverse study population.

Keywords

Ovarian cancer CA125 Predictors Prognosis Biomarker 

Notes

Acknowledgments

The AOV study would like to thank Jennifer Koziak, Mie Konno, Michelle Darago, Faye Chambers and the Tom Baker Cancer Centre Translational Laboratories. The Australian Ovarian Cancer Study Management Group (D. Bowtell, G. Chenevix-Trench, A. deFazio, P. Webb) would like to thank all the clinical and scientific collaborators (see http://www.aocstudy.org/) and the women for their contribution. GCT and PW are supported by Fellowships from NHMRC. The BEL study would like to thank Gilian Peuteman, Thomas Van Brussel, Annick Van den Broeck and Joke De Roover for technical assistance. The SRO study would like to thank all members of Scottish Gynaecological Clinical Trials group and SCOTROC1 investigators.

Funding

Canadian Institutes for Health Research (MOP-86727), U.S. Army Medical Research and Materiel Command (DAMD17-01-1-0729), National Health & Medical Research Council of Australia (199600 and 400281), Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania, Cancer Foundation of Western Australia (Multi-State Application Numbers 191, 211 and 182); Nationaal Kankerplan, National Institutes of Health (R01-CA58598, R01-CA61107, R01-CA122443, R01-CA193965, R01-CA54419, P30-CA15083, P50-CA136393, N01-CN-55424 and N01-PC-67001), Grant-in-Aid for the Third Term Comprehensive 10-Year Strategy for Cancer Control from the Ministry of Health, Labour and Welfare, American Cancer Society Early Detection Professorship (SIOP-06-258-01-COUN), National Center for Advancing Translational Sciences (NCATS), Grant UL1TR000124; Danish Cancer Society (94 222 52), Danish Mermaid I project, Mayo Foundation; Minnesota Ovarian Cancer Alliance, Fred C. and Katherine B. Andersen Foundation, Sherie Hildreth Ovarian Cancer Foundation, Herlev Hospitals Forskningsråd, Direktør Jacob Madsens og Hustru Olga Madsens fond, Arvid Nilssons fond, Gangsted fonden, Herlev Hospitals Forskningsråd, Cancer Research UK (C536/A13086, C536/A6689) and Imperial Experimental Cancer Research Centre (C1312/A15589).

Supplementary material

10552_2016_841_MOESM1_ESM.docx (52 kb)
Supplementary material 1 (DOCX 52 kb)

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Copyright information

© Springer International Publishing Switzerland 2016

Authors and Affiliations

  • Ana Babic
    • 1
  • Daniel W. Cramer
    • 2
    • 3
  • Linda E. Kelemen
    • 4
  • Martin Köbel
    • 5
  • Helen Steed
    • 6
  • Penelope M. Webb
    • 7
    • 8
  • Sharon E. Johnatty
    • 9
  • Anna deFazio
    • 10
    • 11
  • Diether Lambrechts
    • 12
    • 13
  • Marc T. Goodman
    • 14
    • 15
  • Florian Heitz
    • 16
    • 17
  • Keitaro Matsuo
    • 18
  • Satoyo Hosono
    • 19
  • Beth Y. Karlan
    • 20
  • Allan Jensen
    • 21
  • Susanne K. Kjær
    • 21
    • 22
  • Ellen L. Goode
    • 23
  • Tanja Pejovic
    • 24
    • 25
  • Melissa Moffitt
    • 24
    • 25
  • Estrid Høgdall
    • 21
    • 26
  • Claus Høgdall
    • 27
  • Iain McNeish
    • 28
  • Kathryn L. Terry
    • 2
    • 3
    Email author
  1. 1.Dana Farber Cancer Institute and Harvard Medical SchoolBostonUSA
  2. 2.Obstetrics and Gynecology Epidemiology CenterBrigham and Women’s Hospital and Harvard Medical SchoolBostonUSA
  3. 3.Department of EpidemiologyHarvard T.H. Chan School of Public HealthBostonUSA
  4. 4.Department of Public Health SciencesMedical University of South CarolinaCharlestonUSA
  5. 5.Department of Pathology and Laboratory MedicineUniversity of Calgary, Foothills Medical CenterCalgaryCanada
  6. 6.Division of Gynecologic Oncology, Department of Obstetrics and GynecologyRoyal Alexandra HospitalEdmontonCanada
  7. 7.Population Health DepartmentQIMR Berghofer Medical Research InstituteBrisbaneAustralia
  8. 8.Australian Ovarian Cancer Study GroupPeter MacCallum Cancer CentreMelbourneAustralia
  9. 9.Genetics and Computational Biology DepartmentQIMR Berghofer Medical Research InstituteBrisbaneAustralia
  10. 10.Centre for Cancer Research, The Westmead Institute for Medical ResearchThe University of SydneySydneyAustralia
  11. 11.Department of Gynaecological OncologyWestmead HospitalSydneyAustralia
  12. 12.Vesalius Research Center, VIBLouvainBelgium
  13. 13.Laboratory for Translational Genetics, Department of OncologyUniversity of LeuvenLouvainBelgium
  14. 14.Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesUSA
  15. 15.Department of Biomedical Sciences, Community and Population Health Research InstituteCedars-Sinai Medical CenterLos AngelesUSA
  16. 16.Department of Gynecology and Gynecologic OncologyKliniken Essen-Mitte/Evang. Huyssens-Stiftung/Knappschaft GmbHEssenGermany
  17. 17.Department of Gynecology and Gynecologic OncologyDr. Horst Schmidt Kliniken WiesbadenWiesbadenGermany
  18. 18.Division of Molecular MedicineAichi Cancer Center Research InstituteNagoyaJapan
  19. 19.Division of Epidemiology and PreventionAichi Cancer Center Research InstituteNagoyaJapan
  20. 20.Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer InstituteCedars-Sinai Medical CenterLos AngelesUSA
  21. 21.Department of Virus, Lifestyle and GenesDanish Cancer Society Research CenterCopenhagenDenmark
  22. 22.Department of Gynaecology, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  23. 23.Division of Epidemiology, Department of Health Science ResearchMayo ClinicRochesterUSA
  24. 24.Department of Obstetrics and GynecologyOregon Health and Science UniversityPortlandUSA
  25. 25.Knight Cancer InstituteOregon Health and Science UniversityPortlandUSA
  26. 26.Molecular Unit, Department of Pathology, Herlev HospitalUniversity of CopenhagenCopenhagenDenmark
  27. 27.The Juliane Marie Centre, Department of Gynecology, RigshospitaletUniversity of CopenhagenCopenhagenDenmark
  28. 28.Institute of Cancer SciencesUniversity of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer ResearchGlasgowUK

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