title: Hormonal and reproductive risk factors for epithelial ovarian cancer by tumor aggressiveness.
abstract: BACKGROUND
  Approximately half of epithelial ovarian cancers are fatal within 3 years; however, roughly 35% of women survive for at least 10 years. In the Nurses' Health Study, New England Case-Control Study, Australian Ovarian Cancer Study, and NIH-AARP Diet and Health Study, we investigated potential differences in the associations with ovarian cancer risk factors by tumor aggressiveness, defined on the basis of time from diagnosis until death.
  
  
  METHODS
  We calculated relative risks (RR) and 95% confidence intervals (CI) for associations of known or suspected ovarian cancer risk factors with rapidly fatal (death within 3 years of diagnosis) and less aggressive tumors (all others) using Cox proportional hazards competing risks analysis (NHS and AARP) or polytomous logistic regression (NECC, AOCS). Results were combined using random effects meta-analysis.
  
  
  RESULTS
  Increasing age was associated with greater risk of rapidly fatal versus less aggressive disease (RR, 5-year increase: 1.39; 95% CI, 1.29-1.49 vs. RR, 1.09; 95% CI, 1.03-1.16, respectively; Pdiff < 0.0001). Oral contraceptive use was associated with a greater decreased risk of rapidly fatal (RR, 5-year increase: 0.69; 95% CI, 0.58-0.82) versus less aggressive disease (RR, 0.81; 95% CI, 0.74-0.89; Pdiff, 0.002). Conversely, increasing parity was associated only with less aggressive disease (RR per child, 0.87; 95% CI, 0.81-0.93).
  
  
  CONCLUSIONS
  In this analysis of 4,342 cases, there were clear differences in risk factors for rapidly fatal versus less aggressive ovarian tumors.
  
  
  CONCLUSIONS
  Differences in risk factor associations by tumor aggressiveness suggests the developmental pathways through which the tumors develop and may be important for developing primary preventive strategies for the most aggressive cancers.
authors: Corresponding Author: Elizabeth M. Poole, Channing Laboratory, 181 Longwood Ave, 3rd Floor, Boston, MA 02115, USA. nhlip@channing.harvard.edu
authors: Elizabeth M
authors: EM
authors: Poole
authors: Melissa A
authors: MA
authors: Merritt
authors: Susan J
authors: SJ
authors: Jordan
authors: Hannah P
authors: HP
authors: Yang
authors: Susan E
authors: SE
authors: Hankinson
authors: Yikung
authors: Y
authors: Park
authors: Bernard
authors: B
authors: Rosner
authors: Penelope M
authors: PM
authors: Webb
authors: Daniel W
authors: DW
authors: Cramer
authors: Nicolas
authors: N
authors: Wentzensen
authors: Kathryn L
authors: KL
authors: Terry
authors: Shelley S
authors: SS
authors: Tworoger
mesh_terms: D000328:Adult; D000368:Aged; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000009:adverse effects*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007044:Hysterectomy / Q000401:mortality*; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009367:Neoplasm Staging; D009375:Neoplasms, Glandular and Epithelial / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D009511:New England / Q000453:epidemiology; D009726:Nurses; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000209:etiology* / Q000401:mortality; D010298:Parity; D011247:Pregnancy; D011379:Prognosis; D011446:Prospective Studies; D017584:Reproductive History; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
chemical_list: D003276:Contraceptives, Oral