Ovarian cancer is the leading cause of death, among the gynecologic malignancies, and fifth leading cause of death, among cancers in women overall. These statistics largely reflect the fact that most women are diagnosed with ovarian cancer in advanced stages associated with poorer survival. With no certain method for primary prevention, early detection offers the best opportunity for immediately reducing mortality from this disease. However, pelvic ultrasound is costly, may lead to surgery for non-cancerous cysts, and may miss early lesions. Tumor markers, such as CA 125, adapted for screening also have uncertain sensitivity for early stage disease. In this application, investigators at the Brigham and Women's Hospital and Massachusetts General Hospital in Boston and St. Bartholomew's Hospital in London have and will further develop a variety of epidemiologic/specimen banks and pursue new approaches to the identification of serologic markers for ovarian cancer. The epidemiologic/specimen banks include: 1) epidemiologic data, plasma, buffy coat, and red cells from population-based case- control studies of women with newly diagnosed ovarian cancer; 2) epidemiologic data, pre-operative serum and plasma, and fresh frozen tissue on women with early stage ovarian cancer; 3) epidemiologic data, serum, and plasma from women who request genetic testing or who come to prophylatic oophorectomy through familial ovarian cancer clinics in Boston and London; and 4) epidemiologic data and sera from a population-based, longitudinal study designed to assess markers for the early detection of ovarian cancer. These data and specimens will be available both to Early Detection Research Network (EDRN) members as well as co- investigators within our project to pursue an integrated and novel approach to the early detection of ovarian cancer. Our approach will involve: 1) use of Surface-Enhanced Laser Desorption/Ionization (SELDI) mass spectrometry to screen for protein biomarkers that distinguish women with ovarian cancer from those without it or neoplastic from normal tissue; 2) development of statistical methods for combining multiple markers for ovarian cancer to identify panels of biomarkers with superior operating characteristics compared to any single biomarker; 3) purification, sequencing, and recombinant production of the most promising candidate panel of biomarkers to develop a high throughput ELISA or SELDI test kits; 4) assays of the most promising panel of biomarkers in the most informative specimens in the longitudinal screening database; and 5) generalization of statistical techniques to longitudinally measured data. Together with EDRN collaborators, our goal is to develop strategies for the early detection of ovarian cancer that are practical and efficient and can be projected to offer the best opportunity to reduce the mortality from a major cancer in women.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01CA086381-04
Application #
6633741
Study Section
Special Emphasis Panel (ZCA1-SRRB-Y (J1))
Program Officer
Srivastava, Sudhir
Project Start
2000-05-10
Project End
2005-02-28
Budget Start
2003-05-15
Budget End
2004-02-29
Support Year
4
Fiscal Year
2003
Total Cost
$971,206
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Dicks, Ed; Song, Honglin; Ramus, Susan J et al. (2017) Germline whole exome sequencing and large-scale replication identifies FANCM as a likely high grade serous ovarian cancer susceptibility gene. Oncotarget 8:50930-50940
Song, Honglin; Dicks, Ed; Ramus, Susan J et al. (2015) Contribution of Germline Mutations in the RAD51B, RAD51C, and RAD51D Genes to Ovarian Cancer in the Population. J Clin Oncol 33:2901-7
Anderson, Karen S; Cramer, Daniel W; Sibani, Sahar et al. (2015) Autoantibody signature for the serologic detection of ovarian cancer. J Proteome Res 14:578-86
Widschwendter, Martin; Burnell, Matthew; Fraser, Lindsay et al. (2015) Osteoprotegerin (OPG), The Endogenous Inhibitor of Receptor Activator of NF-?B Ligand (RANKL), is Dysregulated in BRCA Mutation Carriers. EBioMedicine 2:1331-9
Nolen, Brian M; Lokshin, Anna E (2013) Biomarker testing for ovarian cancer: clinical utility of multiplex assays. Mol Diagn Ther 17:139-46
Rosenthal, Adam N; Fraser, Lindsay; Manchanda, Ranjit et al. (2013) Results of annual screening in phase I of the United Kingdom familial ovarian cancer screening study highlight the need for strict adherence to screening schedule. J Clin Oncol 31:49-57
Nolen, Brian M; Orlichenko, Lidiya S; Marrangoni, Adele et al. (2013) An extensive targeted proteomic analysis of disease-related protein biomarkers in urine from healthy donors. PLoS One 8:e63368
Cramer, Daniel W (2012) The epidemiology of endometrial and ovarian cancer. Hematol Oncol Clin North Am 26:1-12
Cramer, Daniel W; Bast Jr, Robert C; Berg, Christine D et al. (2011) Ovarian cancer biomarker performance in prostate, lung, colorectal, and ovarian cancer screening trial specimens. Cancer Prev Res (Phila) 4:365-74
Zhu, Claire S; Pinsky, Paul F; Cramer, Daniel W et al. (2011) A framework for evaluating biomarkers for early detection: validation of biomarker panels for ovarian cancer. Cancer Prev Res (Phila) 4:375-83

Showing the most recent 10 out of 45 publications