title: Reproductive characteristics in relation to ovarian cancer risk by histologic pathways.
abstract: OBJECTIVE
  Do reproductive risk factor associations differ across subgroups of invasive epithelial ovarian cancer (EOC) defined by the dualistic model (type I/II) or a histologic pathway-based classification?
  
  
  CONCLUSIONS
  Associations with parity, history of endometriosis, tubal ligation and hysterectomy were found to differ in the context of the type I/II and the histologic pathways classification of ovarian cancer.
  
  
  BACKGROUND
  Shared molecular alterations and candidate precursor lesions suggest that tumor histology and grade may be used to classify ovarian tumors into likely etiologic pathways.
  
  
  METHODS
  This case-control study included 1571 women diagnosed with invasive EOC and 2100 population-based controls that were enrolled from 1992 to 2008. Reproductive risk factors as well as other putative risk factors for ovarian cancer were assessed through in-person interviews.
  
  
  METHODS
  Eligible cases were diagnosed with incident ovarian cancer, were aged 18 and above and resided in eastern Massachusetts or New Hampshire, USA. Controls were identified through random digit dialing, drivers' license and town resident lists and were frequency matched with the cases based on age and study center.
  
  
  RESULTS
  We used polytomous logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for type I/II EOC or using a pathway-based grouping of histologic subtypes. In multivariate analyses, we observed that having a history of endometriosis (OR = 1.92, 95% CI: 1.36-2.71) increased the risk for a type I tumor. Factors that were strongly inversely associated with risk for a type I tumor included parity (≥ 3 versus 0 children, OR = 0.15, 95% CI: 0.11-0.21), having a previous tubal ligation (OR = 0.40, 95% CI: 0.26-0.60) and more weakly hysterectomy (OR = 0.71, 95% CI: 0.45-1.13). In analyses of histologic pathways, parity (≥ 3 versus 0 children, OR = 0.13, 95% CI: 0.10-0.18) and having a previous tubal ligation (OR = 0.41, 95% CI: 0.28-0.60) or hysterectomy (OR = 0.54, 95% CI: 0.34-0.86) were inversely associated with risk of endometrioid/clear cell tumors. Having a history of endometriosis strongly increased the risk for endometrioid/clear cell tumors (OR = 2.41, 95% CI: 1.78-3.26). We did not observe significant differences in the risk associations across these tumor classifications for age at menarche, menstrual cycle length or infertility.
  
  
  CONCLUSIONS
  A potential limitation of this study is that dividing the cases into subgroups may limit the power of these analyses, particularly for the less common tumor types. Since cases were enrolled after their diagnosis, it is possible that the most aggressive cases were not included in the study.
  
  
  CONCLUSIONS
  This study provides insights about the role of reproductive factors in relation to risk of pathway-based subgroups of ovarian cancer that with further confirmation may assist with the development of improved strategies for the prevention of these different tumor types.
  
  
  BACKGROUND
  This research is funded by grants from the National Cancer Institute, the Department of Defense Ovarian Cancer Research Program and the Ovarian Cancer Research Fund. The authors have no competing interests to declare.
  
  
  BACKGROUND
  Not applicable.
authors: Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA. merritt@jimmy.harvard.edu
authors: M A
authors: MA
authors: Merritt
authors: M
authors: M
authors: De Pari
authors: A F
authors: AF
authors: Vitonis
authors: L J
authors: LJ
authors: Titus
authors: D W
authors: DW
authors: Cramer
authors: K L
authors: KL
authors: Terry
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D003276:Contraceptives, Oral / Q000627:therapeutic use; D004715:Endometriosis / Q000150:complications / Q000473:pathology; D005260:Female; D005298:Fertility; D006801:Humans; D007044:Hysterectomy; D007246:Infertility / Q000150:complications; D007434:Intrauterine Devices; D008875:Middle Aged; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000150:complications / Q000175:diagnosis* / Q000473:pathology*; D012044:Regression Analysis; D017584:Reproductive History; D012307:Risk Factors
chemical_list: D003276:Contraceptives, Oral