Aspirin, nonaspirin nonsteroidal anti-inflammatory drug, and acetaminophen use and risk of invasive epithelial ovarian cancer: a pooled analysis in the Ovarian Cancer Association Consortium

Abstract

Background: Regular aspirin use is associated with reduced risk of several malignancies. Epidemiologic studies analyzing aspirin, nonaspirin nonsteroidal anti-inflammatory drug (NSAID), and acetaminophen use and ovarian cancer risk have been inconclusive.

Methods: We analyzed pooled data from 12 population-based case-control studies of ovarian cancer, including 7776 case patients and 11843 control subjects accrued between 1992 and 2007. Odds ratios (ORs) for associations of medication use with invasive epithelial ovarian cancer were estimated in individual studies using logistic regression and combined using random effects meta-analysis. Associations between frequency, dose, and duration of analgesic use and risk of ovarian cancer were also assessed. All statistical tests were two-sided.

Results: Aspirin use was associated with a reduced risk of ovarian cancer (OR = 0.91; 95% confidence interval [CI] = 0.84 to 0.99). Results were similar but not statistically significant for nonaspirin NSAIDs, and there was no association with acetaminophen. In seven studies with frequency data, the reduced risk was strongest among daily aspirin users (OR = 0.80; 95% CI = 0.67 to 0.96). In three studies with dose information, the reduced risk was strongest among users of low dose (<100 mg) aspirin (OR = 0.66; 95% CI = 0.53 to 0.83), whereas for nonaspirin NSAIDs, the reduced risk was strongest for high dose (≥500 mg) usage (OR = 0.76; 95% CI = 0.64 to 0.91).

Conclusions: Aspirin use was associated with a reduced risk of ovarian cancer, especially among daily users of low-dose aspirin. These findings suggest that the same aspirin regimen proven to protect against cardiovascular events and several cancers could reduce the risk of ovarian cancer 20% to 34% depending on frequency and dose of use.

Figure 1.

The summary odds ratios (ORs) and 95% confidence intervals (CIs) for the association between regular (at least once per week) use of aspirin (A), nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) (B), and acetaminophen (C) and ovarian cancer risk. Summary odds ratios and 95% confidence intervals were estimated using a random-effect meta-analytic model. All statistical tests were two-sided. I ² is the percentage of variation across studies due to heterogeneity rather than chance. % Weight describes the weight (inverse variance) each study contributed to the summary odds ratio, and the size of the surrounding square is an illustrative representation of study weighting. The horizontal lines represent study-specific confidence intervals; if ending in an arrow, this indicates that the interval transcends the region plotted. The diamond represents the summary odds ratio and 95% confidence interval. Studies are presented in order of median year of case accrual from earliest to most recent. AUS = Australian Ovarian Cancer Study, Australian Cancer Study; CON = Connecticut Ovary Study; DOV = Diseases of the Ovary and their Evaluation Study; HAW = Hawaii Ovarian Cancer Study; HOP = Hormones and Ovarian Cancer Prediction Study; MAL = Malignant Ovarian Cancer Study; NCO = North Carolina Ovarian Cancer Study; NEC = New England Case–Control Study of Ovarian Cancer; NJO = New Jersey Ovarian Cancer Study; UCI = University of California, Irvine Ovarian Cancer Study; UKO = United Kingdom Ovarian Cancer Population Study; USC = University of Southern California Study of Lifestyle and Women’s Health.