Association of aspirin and ibuprofen use with endometrial cancer risk in the <scp>PLCO</scp> dataset

Given the increasing incidence of endometrial cancer (EC) and the lack of improvement in survival rates, it is imperative to explore possible prevention methods. Studies on aspirin's effect on EC risk have been controversial; research on ibuprofen remains limited. We therefore aimed to investigate the relationship between aspirin and ibuprofen use and risk of EC through a cohort study. This analysis was based on the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, which recruited participants aged 55-74 years from 1993 to 2001, with follow-up for cancer incidence continuing until December 31, 2009. A total of 42,394 women were enrolled in this analysis, and 678 cases of EC were diagnosed during a median follow-up period of 12.0 years. Compared with an intake of <4 pills per month, the use of ibuprofen ≥30 pills per month significantly reduced EC risk (fully-adjusted hazard ratio [HR], 0.75; 95% confidence interval [CI]: 0.58-0.98), particularly in participants with a history of cardiovascular disease (fully-adjusted HR, 0.57; 95% CI: 0.37-0.87). No evidence was found for an association between aspirin and EC occurrence in the general population (fully-adjusted HR, 0.98; 95% CI: 0.81-1.19), nor in specific subgroups. In conclusion, frequent ibuprofen use, unlike aspirin, was linked to reduced EC risk. This protective effect of ibuprofen was enhanced in women with a history of cardiovascular disease. Additional well-designed, prospective research is needed to validate these findings and explore the underlying mechanisms.