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Cyclin E Overexpression in Epithelial Ovarian Cancer Characterizes an Etiologic Subgroup

Departments of ¹ Community and Family Medicine, ² Biostatistics and Bioinformatics, ³ Pathology, and ⁴ Surgery, ⁵ Duke Comprehensive Cancer Center, ⁶ Department of Obstetrics and Gynecology/Division of Gynecologic Oncology, and ⁷ Institute for Genome Sciences and Policy, Duke University Medical Center, Durham, North Carolina

Requests for reprints: Joellen M. Schildkraut, Department of Community and Family Medicine, Duke University Medical Center, Box 2949, Durham, NC 27710. Phone: 919-681-4761; Fax: 919-681-4766. E-mail: schil001{at}mc.duke.edu

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. (Cancer Epidemiol Biomarkers Prev 2008;17(3):585–93)