Kathryn L. Terry

Background:Given that primary prevention strategies for ovarian cancer, such as surgery and medications, have inherent risks, identifying those at high risk of lethal ovarian cancer is critical. We examined prediagnosis factors and risk of developing and dying from ovarian cancer among cancer-free women. Methods:Analyses were conducted in three 12-year periods from 1980 to 2017 in the Nurses’ Health Study (NHS) and NHSII cohorts. Potential risk factors were reproductive and hormonal variables, endometriosis history, smoking, low-dose aspirin, self-identified race, family history, depression, and adiposity over the life course. We used a multistate survival model to estimate relative risks and 95% lower and upper confidence limits for lethal ovarian cancer among 211,420 cancer-free women, among whom 1,730 developed ovarian cancer and 660 died because of ovarian cancer in the same risk period as diagnosis. Results:Of the 22 exposures evaluated, 10 were associated with lethal ovarian cancer. For example, nulliparity had an amplified association with lethal ovarian cancer (1.62, 1.23–2.13) due to associations with both incidence and mortality in the same direction. Oral contraceptive use ≥10 versus 0 years was associated with lethal ovarian cancer (0.65, 0.43–0.97) primarily due to association with incidence, whereas ≥20 versus 0 pack-years of smoking was associated with lethal ovarian cancer (1.25, 1.02–1.53) primarily due to the mortality relationship. Conclusions:Several reproductive factors, depression, and self-identified race were associated with risk of lethal ovarian cancer. Impact:Evaluations of lethal ovarian cancer risk must consider differential associations of exposures with incidence and mortality.

Supplementary Figure S1 shows a participant flow chart for risk period 1

Supplementary Figure S3 shows a participant flow chart for risk period 3

Supplementary Figure S2 shows a participant flow chart for risk period 2

Supplementary Table S1 shows the years of the questionnaires used to define each exposure variable by risk period and cohort

Supplementary Table S2 shows hazard ratios for risk of ovarian cancer incidence and mortality and the relative risk for lethal ovarian cancer for each exposure variable within each risk period and the weighted average estimates across the risk periods

Supplementary Table S5 shows p-values for heterogeneity for lethal ovarian cancer relative risk estimates in analyses by tumor type and menopausal status

Supplementary Table S3 shows hazard ratios for risk of type 1 ovarian cancer incidence and mortality and the relative risk for lethal type 1 ovarian cancer for each exposure variable within each risk period and the weighted average estimates across the risk periods

Supplementary Table S4 shows hazard ratios for risk of type 2 ovarian cancer incidence and mortality and the relative risk for lethal type 2 ovarian cancer for each exposure variable within each risk period and the weighted average estimates across the risk periods

Supplementary Table S6 shows hazard ratios for risk of ovarian cancer incidence and mortality and the relative risk for lethal ovarian cancer for each exposure variable within each risk period and the weighted average estimates across the risk periods among premenopausal women