Factors that increase risk of ovarian cancer include increasing age and nulliparity, while those that decrease risk include surgical history and use of OCs.[63,64] (Refer to the PDQ summary on Prevention of Ovarian Cancer for more information.) Relatively few studies have addressed the effect of these risk factors in women who are genetically susceptible to ovarian cancer. (Refer to the Reproductive factors section of this summary for more information.)
Ovarian cancer incidence rises in a linear fashion from age 30 years to age 50 years and continues to increase, though at a slower rate, thereafter. Before age 30 years, the risk of developing epithelial ovarian cancer is remote, even in hereditary cancer families.
Nulliparity is consistently associated with an increased risk of ovarian cancer, including among BRCA1/BRCA2 mutation carriers. Risk may also be increased among women who have used fertility drugs, especially those who remain nulligravid.[63,67] Evidence is growing that the use of menopausal HRT is associated with an increased risk of ovarian cancer, particularly in long-time users and users of sequential estrogen-progesterone schedules.[68,69,70,71]
Bilateral tubal ligation and hysterectomy are associated with reduced ovarian cancer risk,[63,72,73] including in BRCA1/BRCA2 mutation carriers. Ovarian cancer risk is reduced more than 90% in women with documented BRCA1 or BRCA2 mutations who chose risk-reducing salpingo-oophorectomy (RRSO). In this same population, prophylactic removal of the ovaries also resulted in a nearly 50% reduction in the risk of subsequent breast cancer.[75,76] (Refer to the Risk-reducing salpingo-oophorectomy section of this summary for more information about these studies.)
Use of OCs for 4 or more years is associated with an approximately 50% reduction in ovarian cancer risk in the general population.[63,64] A majority of, but not all, studies also support OCs being protective among BRCA1/ BRCA2 mutation carriers.[66,77,78,79,80] A meta-analysis of 18 studies including 13,627 BRCA mutation carriers reported a significantly reduced risk of ovarian cancer (SRR, 0.50; 95% CI, 0.33–0.75) associated with OC use. (Refer to the Oral contraceptives section in the Chemoprevention section of this summary for more information.)