title: Cyclin E overexpression in epithelial ovarian cancer characterizes an etiologic subgroup.
abstract: BACKGROUND
  The objective of this study was to determine whether cyclin E overexpression defines an etiologically distinct subgroup of ovarian cancer.
  
  
  METHODS
  We analyzed data from 538 epithelial ovarian cancer cases and 629 controls enrolled in a population-based case-control study. Cyclin E protein overexpression was assessed using immunohistochemistry. Case-control and case-case comparisons were done to evaluate the relationship between cyclin E overexpression and epidemiologic risk factors. Logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (95% CI) while adjusting for potential confounders.
  
  
  RESULTS
  Case-control comparisons showed ovarian cancers with and without cyclin E overexpression have different associations with several epidemiologic risk factors. A dose-response relationship was observed between lifetime ovulatory cycles (LOC) and ovarian cancer that overexpressed cyclin E [OR, 1.8; 95% CI, 1.1-3.0 for moderately high LOC (265-390 cycles) and OR, 2.7; 95% CI, 1.6-4.5 for high LOC (>390 cycles) compared with low LOC (<265 cycles)], but no relationship was seen with cancers that lacked overexpression. The most important components of the LOC variable contributing to the differences in the association with the cyclin E subgroups of ovarian cancer were months of oral contraceptive use and months pregnant.
  
  
  CONCLUSIONS
  Cyclin E overexpression is associated with a high number of LOC, largely influenced by oral contraceptive use and pregnancy. This suggests that cyclin E overexpression is a molecular signature characteristic of ovarian cancer cases that may arise via a pathway that involves ovulation-induced alterations.
authors: Department of Community and Family Medicine, Duke University Medical Center, Box 2949, Durham, NC 27710, USA. schil001@mc.duke.edu
authors: Joellen M
authors: JM
authors: Schildkraut
authors: Patricia G
authors: PG
authors: Moorman
authors: Amy E
authors: AE
authors: Bland
authors: Susan
authors: S
authors: Halabi
authors: Brian
authors: B
authors: Calingaert
authors: Regina
authors: R
authors: Whitaker
authors: Paula S
authors: PS
authors: Lee
authors: Tyler
authors: T
authors: Elkins-Williams
authors: Rex C
authors: RC
authors: Bentley
authors: Jeffrey R
authors: JR
authors: Marks
authors: Andrew
authors: A
authors: Berchuck
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D019927:Cyclin E / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009367:Neoplasm Staging; D009657:North Carolina / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000473:pathology; D012042:Registries; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D019927:Cyclin E