This study examined whether genetic factors modify the association between frequent aspirin use and ovarian cancer risk. The researchers pooled individual-level data from eight population-based case-control studies and included patients and control participants with genetic data and data on frequent aspirin use. The study found that frequent aspirin use was associated with a 13% reduced risk of nonmucinous epithelial ovarian cancer, but the polygenic score (PGS) for nonmucinous ovarian cancer did not modify this association. These results suggest that inherited genetic susceptibility to ovarian cancer based on currently identified common genetic variants does not affect the protective association between frequent aspirin use and ovarian cancer.

The study's findings suggest that aspirin could potentially be used as a chemopreventive agent for ovarian cancer. However, the risk of serious adverse events, such as gastric ulcer and hemorrhagic stroke, and the low incidence of ovarian cancer in the general population limit its use. The authors suggest that future research should continue to explore the role of aspirin use for ovarian cancer prevention in higher-risk individuals, identified by their family history or PGS screening, to improve the risk-benefit profile.

Long-term aspirin use has been associated with an increased risk of gastrointestinal bleeding and ulcers. Furthermore, long-term aspirin use can increase the risk of hemorrhagic stroke, a type of stroke caused by bleeding in the brain. Although the risk of these adverse events is low, they can be serious and potentially life-threatening. Aspirin can also interact with other drugs and increase the risk of bleeding.

The study has significant limitations, including the retrospective case-control design, potential confounding and recall bias, and the inability to test for effect modification by pathogenic variants. However, the researchers carefully adjusted for known potential confounders, and case-control and prospective cohort risk estimates of the association of aspirin with ovarian cancer were similar in their previous study, suggesting minimal recall bias.

Considering the aspirin’s ability to reduce the risk of ovarian cancer and possible complications of its long-term use, it is unclear whether the benefit gained by aspirin use in this setting will provide an overall advantage on the population level or for individuals at a heightened risk of developing ovarian cancer. Further research aimed at identifying the mechanisms behind the reduced risk of ovarian cancer by aspirin use are urgently required and may provide future directions to develop preventive pharmacological interventions.