The mortality rate for women with ovarian cancer is very high, mainly because there is no effective method for early detection and more than two-thirds of patients have late-stage metastatic disease at the time of diagnosis. Our preliminary data suggest that plasma levels of lysophospholipids (LPL) are elevated in ovarian cancer patients, including patients with early stage disease, and thus may be useful in ovarian cancer detection. Our preliminary LPL data also show statistically significant differences in samples obtained preoperatively versus postoperatively, suggesting that some LPL may return to baseline after successful treatment and may be useful in predicting recurrence. Serum proteomic profiles (PP) have also shown early promise for ovarian cancer detection, but further investigation regarding the identity of the discriminatory proteins is needed. Thus far, published findings regarding these promising biomarkers have been based on limited numbers of convenience samples. Prior to initiation of large-scale screening studies, it is imperative to confirm these preliminary findings in carefully controlled population-based studies. We propose a population-based case-control study of 250 women with invasive epithelial ovarian cancer and 250 healthy control women matched to cases based on age, ethnicity, county of residence and menopausal status.
Our aims are to: 1) Estimate the sensitivity and specificity of LPL levels (including LPA, LPI, LPC and S1P) and MALDI-based proteomic profiles for the detection of ovarian cancer, 2) Determine which LPL levels (including LPA, LPI, LPC and S1P) or proteomic profiles, alone or in combination (or in combination with CA125) best discriminate(s) between ovarian cancer and no ovarian cancer and 3) Determine whether LPL levels and/or proteomic profiles are prognostic for disease-free survival in ovarian cancer patients. Use of a well-established population-based ultra-rapid ascertainment network will greatly facilitate the project. The proposed work is expected to contribute directly to development of a blood test for detection of ovarian cancer and management of ovarian cancer patients, and thus may result in improved survival from this deadly disease.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA106414-05
Application #
7628977
Study Section
Epidemiology of Cancer Study Section (EPIC)
Program Officer
Patriotis, Christos F
Project Start
2005-08-01
Project End
2009-11-30
Budget Start
2009-06-05
Budget End
2009-11-30
Support Year
5
Fiscal Year
2009
Total Cost
$279,938
Indirect Cost
Name
H. Lee Moffitt Cancer Center & Research Institute
Department
Type
DUNS #
139301956
City
Tampa
State
FL
Country
United States
Zip Code
33612
Lu, Yingchang; Beeghly-Fadiel, Alicia; Wu, Lang et al. (2018) A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk. Cancer Res 78:5419-5430
Praestegaard, Camilla; Jensen, Allan; Jensen, Signe M et al. (2017) Cigarette smoking is associated with adverse survival among women with ovarian cancer: Results from a pooled analysis of 19 studies. Int J Cancer 140:2422-2435
Minlikeeva, Albina N; Freudenheim, Jo L; Eng, Kevin H et al. (2017) History of Comorbidities and Survival of Ovarian Cancer Patients, Results from the Ovarian Cancer Association Consortium. Cancer Epidemiol Biomarkers Prev 26:1470-1473
Kar, Siddhartha P; Adler, Emily; Tyrer, Jonathan et al. (2017) Enrichment of putative PAX8 target genes at serous epithelial ovarian cancer susceptibility loci. Br J Cancer 116:524-535
Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2 (see original citation for additional authors) (2016) No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. Gynecol Oncol 141:386-401
Somiari, Richard I; Sutphen, Rebecca; Renganathan, Kutralanathan et al. (2016) A Low-density Antigen Array for Detection of Disease-associated Autoantibodies in Human Plasma. Cancer Genomics Proteomics 13:13-9
Lawrenson, Kate (see original citation for additional authors) (2016) Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus. Nat Commun 7:12675
Hampras, Shalaka S; Sucheston-Campbell, Lara E; Cannioto, Rikki et al. (2016) Assessment of variation in immunosuppressive pathway genes reveals TGFBR2 to be associated with risk of clear cell ovarian cancer. Oncotarget 7:69097-69110
Richards, Edward J; Permuth-Wey, Jennifer; Li, Yajuan et al. (2015) A functional variant in HOXA11-AS, a novel long non-coding RNA, inhibits the oncogenic phenotype of epithelial ovarian cancer. Oncotarget 6:34745-57
Kar, Siddhartha P; Tyrer, Jonathan P; Li, Qiyuan et al. (2015) Network-Based Integration of GWAS and Gene Expression Identifies a HOX-Centric Network Associated with Serous Ovarian Cancer Risk. Cancer Epidemiol Biomarkers Prev 24:1574-84

Showing the most recent 10 out of 45 publications