Cyclin E overexpression in epithelial ovarian cancer characterizes an etiologic subgroup.
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.
Schildkraut
Joellen M
JM
Department of Community and Family Medicine, Duke University Medical Center, Box 2949, Durham, NC 27710, USA. schil001@mc.duke.edu
Moorman
Patricia G
PG
Bland
Amy E
AE
Halabi
Susan
S
Calingaert
Brian
B
Whitaker
Regina
R
Lee
Paula S
PS
Elkins-Williams
Tyler
T
Bentley
Rex C
RC
Marks
Jeffrey R
JR
Berchuck
Andrew
A
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
D019927:Cyclin E