Ovarian Cancer Cohort Consortium (OC3)

Lead Investigators: Shelley Tworoger (tworoges@ohsu.edu), Nicolas Wentzensen (wentzenn@mail.nih.gov), Renee Fortner (Renee.Turzanski.Fortner@kreftregisteret.no), Britton Trabert (britton.trabert@hci.utah.edu)
Project Coordinator/Point of Contact: Mary Townsend (townsmar@ohsu.edu)

Funding applications are ongoing.

Initial funding was received from the DOD Ovarian Cancer Research Program Translational Leverage Award; PI: Shelley Tworoger

The initial DOD grant provided initial start-up funding to get questionnaire and pathologic data for setting up the OC3 and for completing the described aims. In the future, other grants in the OC3 framework (including grants for generating new biomarker data) will greatly benefit from this initial harmonization of questionnaire data.

Ovarian cancer has a poorly understood etiology and natural history and is the most common cause of death among women who develop gynecologic malignancies and the fifth leading cause of cancer death in females in the US. Although relatively uncommon, the high mortality rate makes the disease a major health concern. Thus, strategies are needed that focus on understanding ovarian cancer risk factors by histotype as well as strategies to identify modifiable risk factors that may provide meaningful reductions in deaths attributable to ovarian cancer.

The objective of this organ-site specific consortium situated within the Cohort Consortium is to study the etiologic heterogeneity of ovarian cancer in multiple cohorts and to build the infrastructure of the Ovarian Cancer Cohort Consortium (OC3), an international consortium of cohort studies, to address scientific aims important for understanding ovarian cancer risk, early detection, and tumor heterogeneity that are only feasible in a consortium setting.

Initially, we propose to evaluate associations of ovarian cancer risk factors by tumor heterogeneity using pooled data from at least 21 cohorts. We will evaluate the following specific aims:
1. Associations of risk factors with invasive ovarian cancer, including (but not limited to) age, OCs, tubal ligation, parity, postmenopausal hormone use, family history of ovarian cancer, BMI, height, analgesic use, and lifetime ovulatory cycles, differ by:
(a) Histologic subtype
(b) Tumor dominance (as a surrogate for cell of origin)
(c) Tumor aggressiveness (tumors fatal within three years vs. all others)

2. Develop ovarian cancer risk prediction models accounting for differential associations by cancer phenotype.

In addition to addressing these important questions, the proposed efforts will create an infrastructure with a core dataset of important variables for ovarian cancer epidemiology that will be available for future efforts to study ovarian cancer risk, including projects that will use prospectively collected biological specimens.

Full cohort analyses using Stratified Cox Proportional Hazards Regression

Individual cohorts do not have a sufficient case numbers to evaluate risk factor associations by histotype.

50

Incident cases of invasive epithelial ovarian cancer (including fallopian tube and primary peritoneal cancers). Data on histotype, tumor dominance, stage and grade, if available.

Risk factors for ovarian cancer, including reproductive factors (age at menarche, parity, age at first full-term pregnancy, infertility, age at menopause, type of menopause, use of oral contraceptives, use of menopausal hormone therapy), anthropometry, gynecologic surgery (hysterectomy, oophorectomy, tubal ligation), first degree family history of breast and ovarian cancer.

Age at cohort entry (or month/year), age at diagnosis (or month/year), race/ethnicity, education

No