Frequent Aspirin May Reduce Risk of Ovarian Cancer for People With Genetic Susceptibility

Frequent aspirin use may lower the risk of ovarian cancer and is not dependent on genetic susceptibility to the disease, according to a study recently published in JAMA Network Open.

“These results suggest that inherited genetic susceptibility to ovarian cancer based on currently identified common genetic variants does not modify the protective association between frequent aspirin use and ovarian cancer,” the study authors wrote in the paper.

Ovarian cancer is a fatal gynecologic cancer with few modifiable risk factors. Daily aspirin use could be a chemopreventive agent against ovarian cancer, as shown in previous case-control studies looking at daily use for ovarian cancer. The authors of the current study also conducted prior research on the benefits of aspirin for patients with a higher risk of ovarian cancer based on epidemiologic risk factors, including family history of ovarian cancer or obesity.

“While aspirin is a promising chemopreventive agent for ovarian cancer, its use remains limited by several factors,” the study authors wrote. “First, serious adverse events can occur with aspirin use, including gastric ulcer and hemorrhagic stroke; although rare, these risks are nonnegligible. Second, the incidence of ovarian cancer in the general population is low; thus, the number needed to treat to prevent 1 case of ovarian cancer is high.”

The preventative effects of aspirin were not impacted by a number of epidemiologic risk factors, according to their findings. The current study aims to expand on this—investigators used a polygenic score (PGS) to understand a person’s genetic susceptibility to ovarian cancer and if aspirin’s preventative effects were impacted by a person’s genetic disposition.

Investigators pooled the data of participants who were enrolled in 8 population-based case-controlled studies (Ovarian Cancer Association Consortium) between 1995 and 2009. There were 4476 case patients and 6659 control participants in the study population, and 86% from both arms had available genotype data, which were evaluated by the PGS.

Frequent aspirin use was associated with a 13% lower risk of nonmucinous ovarian cancer, consistent with previous studies. PNG evaluation showed that inherited genetic susceptibility based on current identified common genetic variants did not reduce the protective association between aspirin and ovarian cancer.

In a subgroup analysis, daily aspirin appeared to offer the highest risk reduction benefits to patients at risk of high-grade serous and endometrioid tumors. It also sustained risk reduction benefits in people with a PGS score above the median; however, these effects were not maintained for those with a PGS score in the highest quintile.

The study was limited because it used a case-control design that can lead to confounding and recall bias. Additionally, investigators only included patients with available genetic data and did not test for effect modification by pathogenic variants; however, current randomized clinical trials are studying these subsets.

Aspirin may have rare severe adverse events, such as gastric ulcer and hemorrhagic stroke, as seen in previous studies. Incidence of ovarian cancer is relatively low and it could be difficult to determine prevention measures.

“Although we did not observe effect modification on the multiplicative scale, future prospective studies are needed to estimate the absolute benefit of frequent aspirin use for individuals at higher risk of ovarian cancer and to weigh the benefits and harms for all conditions affected by aspirin,” the study authors wrote in the article.

Reference

Hurwitz L, Webb P, Jordan S, et al. Association of Frequent Aspirin Use With Ovarian Cancer Risk According to Genetic Susceptibility. JAMA Netw Open. 2023;6(2):e230666. doi:10.1001/jamanetworkopen.2023.0666