Ovarian Cancer Risk Lower With Daily Aspirin, Despite Genetics

Frequent aspirin intake may reduce a woman’s risk of getting ovarian cancer, regardless of their genetic susceptibility, new research suggests.

The study found that daily or almost daily aspirin use was associated with a 13% reduction in ovarian cancer risk, which was not modified by an individual’s polygenic score (PGS).

“Our findings suggest that frequent use of aspirin is associated with reduced ovarian cancer risk, regardless of whether a woman has lower or higher genetic susceptibility to ovarian cancer, as predicted by a set of known, common risk variants,” said lead author Lauren M. Hurwitz, PhD, MHS, division of cancer epidemiology and genetics at the National Cancer Institute, Rockville, Maryland.

The study was published online February 24 in JAMA Network Open.

Patients diagnosed with ovarian cancer face difficult survival odds, which make preventive strategies especially important. Evidence suggests that frequent aspirin use can reduce the risk for ovarian cancer by about 13%, but it’s unclear whether genetic factors change those odds.

Although promising for chemoprevention, aspirin use can also come with downsides, including gastric ulcer and hemorrhagic stroke, which is why identifying and targeting individuals at higher risk for ovarian cancer who may benefit from frequent aspirin use is important.

In the current analysis, Hurwitz and colleagues used a PGS to determine whether the protective effects of daily or near-daily aspirin use for 6 months or more could be modified by genetics.

The study was a pooled analysis of eight case-controlled studies from the Ovarian Cancer Association Consortium conducted in the United Kingdom, the United States, and Australia over a 14-year period. The researchers looked at genetic data and data on frequent aspirin use among 4476 case patients with nonmucinous ovarian cancer (average age 57) and 6659 control participants (average age 58). Overall, 575 patients (13%) and 1030 controls (15%) reported frequent aspirin use.

The authors used a PGS previously developed using 22 single-nucleotide variants. Because this PGS was developed for nonmucinous epithelial ovarian cancer, only these patients were included in the analysis.

Consistent with previous evidence, the authors found that frequent aspirin use was associated with a 13% lower risk for nonmucinous ovarian cancer (odds ratio [OR], 0.87). And, notably, this association did not differ by PGS. Risk reductions were greatest for high-grade serous (OR, 0.83) and endometrioid tumors (OR, 0.73), with no evidence that PGS modified this association.

Overall, “we observed consistent protective associations between frequent aspirin use and nonmucinous ovarian cancer across strata of genetic susceptibility to ovarian cancer,” the authors conclude. “This work expands on the evidence base to suggest that chemoprevention programs could target individuals at higher risk of ovarian cancer.”

However, the authors noted that they were unable to test for effect modifications by specific pathogenic variants, such as BRCA1 or BRCA2.  

“Our study did not address whether aspirin use is associated with reduced ovarian cancer risk among BRCA or other pathogenic variant carriers, and so our findings should not be used to inform discussions around aspirin use for these specific high-risk groups,” Hurwitz said. “Women with higher genetic susceptibility to ovarian cancer based on these common risk variants should discuss with their doctor the benefits and harms of taking aspirin for disease prevention.”

This study was supported by a grant from the DoD Ovarian Cancer Research Program. Hurwitz reports no relevant financial relationships, but several co-authors did report funding and support. The full list can be found with the original article.

JAMA Netw Open. Published online February 24, 2023. Full text

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