Ana Babic1, Daniel W Cramer2,3, Linda E Kelemen4, Martin Köbel5, Helen Steed6, Penelope M Webb7,8, Sharon E Johnatty9, Anna deFazio10,11, Diether Lambrechts12,13, Marc T Goodman14,15, Florian Heitz16,17, Keitaro Matsuo18, Satoyo Hosono19, Beth Y Karlan20, Allan Jensen21, Susanne K Kjær21,22, Ellen L Goode23, Tanja Pejovic24,25, Melissa Moffitt24,25, Estrid Høgdall21,26, Claus Høgdall27, Iain McNeish28, Kathryn L Terry29,30. 1. Dana Farber Cancer Institute and Harvard Medical School, Boston, MA, USA. 2. Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave, Boston, MA, 02115, USA. 3. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 4. Department of Public Health Sciences, Medical University of South Carolina, Charleston, SC, USA. 5. Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Center, Calgary, AB, Canada. 6. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Royal Alexandra Hospital, Edmonton, AB, Canada. 7. Population Health Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia. 8. Australian Ovarian Cancer Study Group, Peter MacCallum Cancer Centre, 305 Grattan St, Melbourne, VIC, 3000, Australia. 9. Genetics and Computational Biology Department, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD, 4006, Australia. 10. Centre for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Sydney, NSW, Australia. 11. Department of Gynaecological Oncology, Westmead Hospital, Sydney, NSW, Australia. 12. Vesalius Research Center, VIB, Louvain, Belgium. 13. Laboratory for Translational Genetics, Department of Oncology, University of Leuven, Louvain, Belgium. 14. Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 15. Department of Biomedical Sciences, Community and Population Health Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 16. Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte/Evang. Huyssens-Stiftung/Knappschaft GmbH, Essen, Germany. 17. Department of Gynecology and Gynecologic Oncology, Dr. Horst Schmidt Kliniken Wiesbaden, Wiesbaden, Germany. 18. Division of Molecular Medicine, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan. 19. Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Aichi, Japan. 20. Women's Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA. 21. Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, Copenhagen, Denmark. 22. Department of Gynaecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 23. Division of Epidemiology, Department of Health Science Research, Mayo Clinic, Rochester, MN, USA. 24. Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, OR, USA. 25. Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA. 26. Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark. 27. The Juliane Marie Centre, Department of Gynecology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. 28. Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow, UK. 29. Obstetrics and Gynecology Epidemiology Center, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Ave, Boston, MA, 02115, USA. kterry@partners.org. 30. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. kterry@partners.org.
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.
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.
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