A model for estimating ovarian cancer risk: application for preventive oophorectomy.
OBJECTIVE
It is important to identify women in the population who have a high risk of ovarian cancer and who might benefit from prophylactic bilateral salpingo-oophorectomy. The probability that a woman will develop ovarian cancer depends on her current age, her reproductive history and her genetic status.


METHODS
We simulated the distribution of ovarian cancer risk for the 2011 Ontario female population. We generated (at random) individual risks of ovarian cancer to age 80 for 6,301,340 women, based on the published risk factors, mutation frequencies and population age-specific incidence rates (SEER database). Risk factors included parity, breastfeeding, oral contraceptives, tubal ligation and family history. Genetic factors included 11 single nucleotide polymorphisms (SNPs) and BRCA1/2 mutations.


RESULTS
Of the 6,301,340 women simulated as the general population of Ontario, the (complete) model predicts that 65,805 women (1.0%) will develop ovarian cancer by age 80. There were 46,069 women (0.7%) with a risk of ovarian cancer above 5%. BRCA1/2 mutation carriers accounted for 67.4% of the women at greater than 5% risk (31,028 women). Among ovarian cancer patients at greater than 5% risk, a BRCA1/2 mutation was present in 89.2%. In contrast, SNPs contribute to a very small proportion of the ovarian cancer patients who were at greater than 5% risk.


CONCLUSIONS
Approximately 12.9% of all ovarian cancers in Ontario occur in the 0.7% of women in the general population who have a lifetime ovarian cancer risk in excess of 5%, the majority of whom carry a mutation in BRCA1 or BRCA2.
Women's College Research Institute, Women's College Hospital, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
Vasily
V
Giannakeas
Women's College Research Institute, Women's College Hospital, Toronto, Canada.
Victoria
V
Sopik
Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
Konstantin
K
Shestopaloff
Women's College Research Institute, Women's College Hospital, Toronto, Canada.
Javaid
J
Iqbal
Department of Gynecologic Oncology, Princess Margaret Hospital, Toronto, Canada.
Barry
B
Rosen
Women's College Research Institute, Women's College Hospital, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada.
Mohammad
M
Akbari
Women's College Research Institute, Women's College Hospital, Toronto, Canada; Dalla Lana School of Public Health, University of Toronto, Toronto, Canada. Electronic address: steven.narod@wchospital.ca.
Steven A
SA
Narod
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001942:Breast Feeding / Q000706:statistics & numerical data; D003198:Computer Simulation; D003278:Contraceptives, Oral, Hormonal / Q000627:therapeutic use; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D005820:Genetic Testing; D061325:Hereditary Breast and Ovarian Cancer Syndrome / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D009864:Ontario / Q000453:epidemiology; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000517:prevention & control*; D010052:Ovariectomy / Q000379:methods*; D010298:Parity; D020641:Polymorphism, Single Nucleotide; D065286:Prophylactic Surgical Procedures / Q000379:methods*; D016016:Proportional Hazards Models; D018570:Risk Assessment; D058994:Salpingectomy / Q000379:methods*; D013246:Sterilization, Tubal / Q000706:statistics & numerical data
D003278:Contraceptives, Oral, Hormonal
Genetic testing; Oophorectomy; Ovarian cancer; SNPs