Type 1 and Type 2 ovarian cancer in the PLCO Trial
Demographic and clinical differences will be examined:
Age, gravity, and parity.
Ethnic group
Area of residence/testing center
Positive family history of breast or ovarian cancer
Personal history of breast cancer
Use of aspirin or ibuprofen
Use of birth control pills
History of endometriosis
Use of menopausal hormone replacement
Prior gynecologic procedures:
Hysterectomy
Tubal ligation
Ectopic pregnancy
Outcome:
Mortality/survival
Stage at diagnosis.
We plan to assess the above risk factors to determine if there are significant differences between patients with type 1 and type 2 cancers.
Mortality and survival for the screening group and control group will also be analyzed to assess the impact of screening on type 1 and type 2 ovarian cancer. We would also like to assess for differences in stage at presentation for type 1 and 2 ovarian cancer.
OBJECTIVE: Examine differences between type 1 and type 2 ovarian cancer in the PLCO trial.
BACKGROUND: Recent molecular evidence suggests two different pathways are involved in ovarian carcinogenesis. Epithelial ovarian cancers are now broadly divided into type 1 and type 2, based on the histopathologic characteristics and underlying genetic changes. Type 1 cancers (endometrioid, clear cell, and mucinous) are associated with endometriosis and associated with mutations in specific genetic pathways, ie. PTEN, KRAS, BRAF, ARID1A, and PIK3CA. Type 2 cancers (high grade serous cancers and undifferentiated cancers) are hypothesized to arise from tubal epithelium, secondarily implant on the ovarian surface, and are associated with mutations in TP53 and the BRCA pathway. Implicit in this model is both type 1 and type 2 malignancies may originate from extraovarian sites; type 1 from endometrosis and retrograde menstruation, and type 2 from the distal fallopian tube. Also, clinical observations suggest that type 1 malignancies grow locally and metastasize late in the clinical course; type 2 malignancies seem to metastasize early. This hypothesis has important implications, both for prevention and for screening. The current study aims to differentiate risk factors for type 1 versus type 2 ovarian cancer. We also plan to review the survival data with respect to type 1 and type 2 cancer to assess whether screening may be more efficacious in either type.
Bruce Kessel, M.D.
University of Hawaii John A. Burns School of Medicine
Heung Jun Ahn, Ph.D.
University of Hawaii John A. Burns School of Medicine