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Risk Factors for Ovarian Cancers With and Without Microsatellite Instability

Segev, Yakir MD*†‡; Pal, Tuya MD; Rosen, Barry MD†‡; McLaughlin, John R. PhD§; Sellers, Thomas A. PhD; Risch, Harvey A. MD, PhD; Zhang, Shiyu PhD*; Sun, Ping PhD*; Narod, Steven A. MD, PhD*; Schildkraut, Joellen PhD#

International Journal of Gynecological Cancer: May 2014 - Volume 24 - Issue 4 - p 664–669
doi: 10.1097/IGC.0000000000000134
Ovarian Cancer

Objective: In a population-based sample of epithelial ovarian cancers, the objective of this study was to evaluate the association between microsatellite instability (MSI) status and the following factors: (1) ovarian cancer risk factors and (2) the distribution of the specific histologic subtypes.

Patients and Methods: Participants were drawn from 3 population-based studies of primary epithelial ovarian cancer; tumor DNA was analyzed using 5 standardized microsatellite markers to assess the MSI status. Patients were divided into 3 groups (MSI-high, MSI-low, and MSI-stable) according to the National Cancer Institute criteria. We compared the prevalence of specific known risk and protective factors among the 3 subgroups, including body mass index, smoking history, parity, BRCA1 and BRCA2 mutation status, past oral contraceptive use, and tubal ligation. Similarly, we compared the distribution of the histologic subtypes among the 3 subgroups.

Results: A total of 917 ovarian cancer patients were included. One hundred twenty-seven cases of cancer (13.8%) were MSI-high. Subgroup analyses according to smoking, body mass index, parity, past oral contraceptive use, and past tubal ligation did not reveal any statistically significant differences among the groups. Among the 29 patients with BRCA1 mutations, 20.7% had MSI-high cancers compared with 5.9% among 17 patients with BRCA2 mutations. The proportions of different ovarian cancer histologies among the various MSI subgroups were similar.

Conclusions: The prevalence of risk and protective factors among ovarian cancer patients is similar for cancers with and without MSI. The distributions of MSI do not differ significantly among ovarian cancers with different histologies. Ovarian cancer patients with BRCA1 mutations had a 21% rate of MSI-high tumors compared with 6% among patients with BRCA2 mutations, but this difference was not statistically significant.

*Familial Breast Cancer Research, Women’s College Research Institute; †Department of Obstetrics and Gynecology, University of Toronto; ‡Department of Gynecologic Oncology, Princess Margaret Hospital; §Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada; ∥Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, FL; ¶Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT; and #Duke University, Duke School of Medicine, Durham, NC.

Address correspondence and reprint requests to Steven A. Narod, MD, Familial Breast Cancer Research, Women’s College Research Institute, 790 Bay St, 7th floor, Toronto, Ontario, Canada M5G 1N8. E-mail: steven.narod@wchospital.ca.

The authors declare no conflicts of interest.

Received February 27, 2013

Accepted May 5, 2013

© 2014 by the International Gynecologic Cancer Society and the European Society of Gynaecological Oncology.