Association of Analgesic Use With Risk of Ovarian Cancer in the Nurses’ Health Studies

Abstract

Importance: Ovarian cancer is a highly fatal malignancy with few modifiable risk factors. Results from case-control studies have reported a modest reduced risk of ovarian cancer among women who frequently use aspirin or regularly use low-dose aspirin. We sought to confirm these findings in a large, prospective study with detailed information on NSAID use. Objective: To evaluate whether regular aspirin or non-aspirin NSAID use, and patterns of use, are associated with lower ovarian cancer risk. Design: We included women from two prospective cohorts, the Nurses’ Health Study (NHS) and NHSII. Setting: NHS/NHSII participants were followed 1980–2014 (NHS) and 1989–2015 (NHSII). Participants: Participants in NHS (N=93,664) and NHSII (N=111,834), including 1054 cases of incident epithelial ovarian cancer. Exposures: For each analgesic type, aspirin, low-dose aspirin, non-aspirin NSAIDs and acetaminophen, we evaluated timing, duration, frequency, and number of tablets used; exposure information was updated every 2–4 years. Main Outcome(s) and Measure(s): We used Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of aspirin, non-aspirin NSAIDs, and acetaminophen with risk of epithelial ovarian cancer. All statistical tests were two-sided, with a significance level of 0.05. Results: We did not observe significant associations between aspirin and ovarian cancer risk when we evaluated current versus non-use of any aspirin, regardless of dose (HR=0.99, 95%CI=0.83–1.19). However, when we evaluated low-dose (≤100mg) and standard-dose (325mg) aspirin separately, we observed an inverse association for low-dose aspirin (HR=0.77, 95%CI=0.61–0.96), but no association for standard-dose aspirin (HR=1.17, 95%CI=0.92–1.49). Current use of non-aspirin NSAIDs was positively associated with risk of ovarian cancer compared to non-use (HR=1.19, 95%CI=1.00–1.41), and we observed significant positive trends for duration of use (p-trend=0.02) and cumulative average tablets per week (p-trend=0.03). There were no clear associations for acetaminophen. Conclusions and Relevance: Our results were consistent with case-control studies showing a reduced risk of ovarian cancer among regular users of low-dose aspirin. We observed an increased risk of ovarian cancer with long-term high-quantity use of other analgesics, particularly non-aspirin NSAIDs, though this finding requires confirmation.

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