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



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.


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.


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.


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.


Ovarian cancer CA125 Predictors Prognosis Biomarker 



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 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.


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)


  1. 1.
    Yin BW, Dnistrian A, Lloyd KO (2002) Ovarian cancer antigen CA125 is encoded by the MUC16 mucin gene. Int J Cancer 98:737–740CrossRefPubMedGoogle Scholar
  2. 2.
    Anderson GL, McIntosh M, Wu L et al (2010) Assessing lead time of selected ovarian cancer biomarkers: a nested case-control study. J Natl Cancer Inst 102:26–38CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Haridas D, Ponnusamy MP, Chugh S, Lakshmanan I, Seshacharyulu P, Batra SK (2014) MUC16: molecular analysis and its functional implications in benign and malignant conditions. FASEB J 28:4183–4199CrossRefPubMedGoogle Scholar
  4. 4.
    Terry KL, Schock H, Fortner RT et al (2016) A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort. Clin Cancer Res 22:4664–4675CrossRefPubMedGoogle Scholar
  5. 5.
    Cramer DW, Bast RC Jr, Berg CD et al (2011) Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Phila) 4:365–374CrossRefGoogle Scholar
  6. 6.
    Bottoni P, Scatena R (2015) The role of CA 125 as tumor marker: biochemical and clinical aspects. Adv Exp Med Biol 867:229–244CrossRefPubMedGoogle Scholar
  7. 7.
    Buys SS, Partridge E, Black A et al (2011) Effect of screening on ovarian cancer mortality: the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening randomized controlled trial. JAMA 305:2295–2303CrossRefPubMedGoogle Scholar
  8. 8.
    Jacobs IJ, Menon U, Ryan A et al (2016) Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet 387:945–956CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Davidson NG, Khanna S, Kirwan PH, Bircumshaw D (1991) Prechemotherapy serum CA125 level as a predictor of survival outcome in epithelial carcinoma of the ovary. Clin Oncol (R Coll Radiol) 3:32–36CrossRefGoogle Scholar
  10. 10.
    Hogdall E (2008) Cancer antigen 125 and prognosis. Curr Opin Obstet Gynecol 20:4–8CrossRefPubMedGoogle Scholar
  11. 11.
    Rustin GJS, van der Burg MEL, Griffin CL et al (2010) Early versus delayed treatment of relapsed ovarian cancer (MRC OV05/EORTC 55955): a randomised trial. Lancet 376:1155–1163CrossRefPubMedGoogle Scholar
  12. 12.
    Johnson CC, Kessel B, Riley TL et al (2008) The epidemiology of CA-125 in women without evidence of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) screening trial. Gynecol Oncol 110:383–389CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Pauler DK, Menon U, McIntosh M, Symecko HL, Skates SJ, Jacobs IJ (2001) Factors influencing serum CA125II levels in healthy postmenopausal women. Cancer Epidemiol Biomar Prev 10:489–493Google Scholar
  14. 14.
    Westhoff C, Gollub E, Patel J, Rivera H, Bast R Jr (1990) CA 125 levels in menopausal women. Obstet Gynecol 76:428–431PubMedGoogle Scholar
  15. 15.
    Cramer DW, Vitonis AF, Welch WR et al (2010) Correlates of the preoperative level of CA125 at presentation of ovarian cancer. Gynecol Oncol 119:462–468CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Pearce CL, Wu AH, Gayther SA et al (2008) Progesterone receptor variation and risk of ovarian cancer is limited to the invasive endometrioid subtype: results from the Ovarian Cancer Association Consortium pooled analysis. Br J Cancer 98:282–288CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Gayther SA, Song H, Ramus SJ et al (2007) Tagging single nucleotide polymorphisms in cell cycle control genes and susceptibility to invasive epithelial ovarian cancer. Cancer Res 67:3027–3035CrossRefPubMedGoogle Scholar
  18. 18.
    Kelemen LE, Kobel M, Chan A, Taghaddos S, Dinu I (2013) Differentially methylated loci distinguish ovarian carcinoma histological types: evaluation of a DNA methylation assay in FFPE tissue. BioMed Res Int 2013:815894CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Kobel M, Madore J, Ramus SJ et al (2014) Evidence for a time-dependent association between FOLR1 expression and survival from ovarian carcinoma: implications for clinical testing. An Ovarian Tumour Tissue Analysis consortium study. Br J Cancer 111:2297–2307CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Merritt MA, Green AC, Nagle CM, Webb PM (2008) Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer. Int J Cancer 122:170–176CrossRefPubMedGoogle Scholar
  21. 21.
    Song H, Ramus SJ, Tyrer J et al (2009) A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nat Genet 41:996–1000CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Goodman MT, Lurie G, Thompson PJ, McDuffie KE, Carney ME (2008) Association of two common single-nucleotide polymorphisms in the CYP19A1 locus and ovarian cancer risk. Endocr Relat Cancer 15:1055–1060CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Lurie G, Wilkens LR, Thompson PJ et al (2008) Combined oral contraceptive use and epithelial ovarian cancer risk: time-related effects. Epidemiology 19:237–243CrossRefPubMedGoogle Scholar
  24. 24.
    du Bois A, Luck HJ, Meier W et al (2003) A randomized clinical trial of cisplatin/paclitaxel versus carboplatin/paclitaxel as first-line treatment of ovarian cancer. J Natl Cancer Inst 95:1320–1329CrossRefPubMedGoogle Scholar
  25. 25.
    Harter P, Muallem ZM, Buhrmann C et al (2011) Impact of a structured quality management program on surgical outcome in primary advanced ovarian cancer. Gynecol Oncol 121:615–619CrossRefPubMedGoogle Scholar
  26. 26.
    Hirose K, Tajima K, Hamajima N et al (1999) Comparative case-referent study of risk factors among hormone-related female cancers in Japan. Jpn J Cancer Res 90:255–261CrossRefPubMedGoogle Scholar
  27. 27.
    Pharoah PD, Song H, Dicks E, et al (2016) PPM1D mosaic truncating variants in ovarian cancer cases may be treatment-related somatic mutations. J Natl Cancer Inst 108:1–5CrossRefGoogle Scholar
  28. 28.
    Begum FD, Hogdall E, Kjaer SK et al (2009) Preoperative serum tetranectin, CA125 and menopausal status used as single markers in screening and in a risk assessment index (RAI) in discriminating between benign and malignant ovarian tumors. Gynecol Oncol 113:221–227CrossRefPubMedGoogle Scholar
  29. 29.
    Kelemen LE, Sellers TA, Schildkraut JM et al (2008) Genetic variation in the one-carbon transfer pathway and ovarian cancer risk. Cancer Res 68:2498–2506CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Schildkraut JM, Iversen ES, Wilson MA et al (2010) Association between DNA damage response and repair genes and risk of invasive serous ovarian cancer. PLoS ONE 5:e10061CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Terry KL, De Vivo I, Titus-Ernstoff L, Shih MC, Cramer DW (2005) Androgen receptor cytosine, adenine, guanine repeats, and haplotypes in relation to ovarian cancer risk. Cancer Res 65:5974–5981CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Pejovic T, Yates JE, Liu HY et al (2006) Cytogenetic instability in ovarian epithelial cells from women at risk of ovarian cancer. Cancer Res 66:9017–9025CrossRefPubMedGoogle Scholar
  33. 33.
    Pejovic T, Pande NT, Mori M et al (2009) Expression profiling of the ovarian surface kinome reveals candidate genes for early neoplastic changes. Transl Oncol 2:341–349CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Hogdall E, Fung ET, Christensen IJ et al (2010) Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients. Proteom Clin Appl 4:940–952CrossRefGoogle Scholar
  35. 35.
    Vasey PA, Jayson GC, Gordon A et al (2004) Phase III randomized trial of docetaxel-carboplatin versus paclitaxel-carboplatin as first-line chemotherapy for ovarian carcinoma. J Natl Cancer Inst 96:1682–1691CrossRefPubMedGoogle Scholar
  36. 36.
    Marsh S, Paul J, King CR, Gifford G, McLeod HL, Brown R (2007) Pharmacogenetic assessment of toxicity and outcome after platinum plus taxane chemotherapy in ovarian cancer: the Scottish Randomised Trial in Ovarian Cancer. J Clin Oncol 25:4528–4535CrossRefPubMedGoogle Scholar
  37. 37.
    Hosmer DW, Lemeshow S (1989) Applied logistic regression. Wiley, New YorkGoogle Scholar
  38. 38.
    Tworoger SS, Eliassen AH, Sluss P, Hankinson SE (2007) A prospective study of plasma prolactin concentrations and risk of premenopausal and postmenopausal breast cancer. J Clin Oncol 25:1482–1488CrossRefPubMedGoogle Scholar
  39. 39.
    Matsuno RK, Sherman ME, Visvanathan K et al (2013) Agreement for tumor grade of ovarian carcinoma: analysis of archival tissues from the surveillance, epidemiology, and end results residual tissue repository. Cancer Causes Control 24:749–757CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Kobel M, Kalloger SE, Lee S et al (2013) Biomarker-based ovarian carcinoma typing: a histologic investigation in the ovarian tumor tissue analysis consortium. Cancer Epidemiol Biomark Prev 22:1677–1686CrossRefGoogle Scholar
  41. 41.
    Belisle JA, Horibata S, Jennifer GA et al (2010) Identification of Siglec-9 as the receptor for MUC16 on human NK cells, B cells, and monocytes. Mol Cancer 9:118CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Song H, Ramus SJ, Tyrer J et al (2009) A genome-wide association study identifies a new ovarian cancer susceptibility locus on 9p22.2. Nat Genet 41:996–1000CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Olsen CM, Nagle CM, Whiteman DC et al (2013) Obesity and risk of ovarian cancer subtypes: evidence from the Ovarian Cancer Association Consortium. Endocr-Relat Cancer 20:251–262CrossRefPubMedGoogle Scholar
  44. 44.
    Pearce CL, Templeman C, Rossing MA et al (2012) Association between endometriosis and risk of histological subtypes of ovarian cancer: a pooled analysis of case-control studies. Lancet Oncol 13:385–394CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Sieh W, Kobel M, Longacre TA et al (2013) Hormone-receptor expression and ovarian cancer survival: an ovarian tumor tissue analysis consortium study. Lancet Oncol 14:853–862CrossRefPubMedPubMedCentralGoogle Scholar

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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