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Risk Factors for Ovarian Cancers With and Without Microsatellite Instability
  1. Yakir Segev, MD*,,
  2. Tuya Pal, MD*,
  3. Barry Rosen, MD,
  4. John R. McLaughlin, MD,
  5. Thomas A. Sellers, PhD§,
  6. Harvey A. Risch, MD,
  7. Shiyu Zhang, PhD*,
  8. Sun Ping, PhD*,
  9. Steven A. Narod, MD* and
  10. Joellen Schildkraut, PhD
  1. *Women’s College Research Institute, Familial Breast Cancer Research;
  2. Canada Department of Obstetrics and Gynecology, University of Toronto and Gynecologic Oncology, Princess Margaret Hospital; and
  3. Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada;
  4. §Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center, Tampa, FL;
  5. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT; and
  6. Duke University, Duke School of Medicine, Durham, NC.
  1. Address correspondence and reprint requests to Steven A. Narod, MD, Women’s College Research Institute, Familial Breast Cancer Research, 790 Bay St, 7th Floor, Toronto, Ontario, Canada M5G 1N8. E-mail:


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

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 MSI status. Patients were divided into 3 groups (MSI-high, MSI-low, and MSI-stable) according to 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 (13.8%) cancers 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 BRCA2-mutation patients. The proportions of different ovarian cancer histologic findings 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 histologic findings. 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.

  • Ovarian cancer
  • Microsatellite instability
  • Risk factors

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  • The authors declare no conflicts of interest.