Two Studies Offer More Insight on Risk-Reducing Benefits of Low-Dose Aspirin, NSAIDs

Adriana Vidal, PhD

New research on the risk-reducing benefits of aspirin shed more light on its mechanism of action as well as its potential benefit to reduce the risk of aggressive prostate cancer, according to data from two studies presented at the 13th Annual American Association for Cancer Research International Conference on Frontiers in Cancer Prevention Research.

While prior studies measuring aspirin’s abilities to reduce the risk of cancer mortality showed that the agent inhibits the COX-1 pathway, the new study has shown that the agent also plays a role in inhibiting the COX-2 pathway.

“Studies have shown that aspirin administration for 5 or more years reduces the incidence of all cancers by 38%. This benefit is seen even at the low doses of aspirin (eg, 81 mg daily) required to inhibit platelet aggregation via inhibiting the COX-1 pathway, a finding consistent with the known participation of platelets in the metastatic process,” Pierre Massion, MD, professor of medicine and cancer biology in the Division of Allergy, Pulmonary, and Critical Care Medicine at Vanderbilt University School of Medicine, said in a statement.

In this new study, Massion and his colleagues set out to determine if low-dose aspirin reduced levels of the pro-metastatic molecule prostaglandin E2 (PGE2) through inhibition of the COX-2 pathway.

“We found that the potency of low-dose aspirin in inhibiting COX-2 in the tumor cells is as great or greater than its potency as an inhibitor of COX-1 in the platelet,” Massion said. “This indicates that at a cellular level, aspirin is not selective for the platelet, but could also block COX-2 in cancers.”

Using three lung adenocarcinoma cell lines, the researchers found that the doses of aspirin required to inhibit COX-2—dependent PGE2 production were equal to or less than the doses required for the inhibition of COX-1–dependent platelet aggregation.

Next, using urine samples of 54 participants who took the low-dose 81-mg aspirin tablets for 2 weeks, the researchers demonstrated that aspirin inhibited PGE2 production by 45% and reduced the levels of a metabolite of PGE2, prostacyclin, by 37%.

“Our findings may explain how even a very low dose of aspirin taken daily can produce such a substantial reduction in cancer deaths and metastasis,” Massion said.

Role in Aggressive Prostate Cancer

Another study presented at the conference showed that the use of aspirin and/or other non-steroidal anti-inflammatory drugs (NSAIDs) was associated with a reduced risk for aggressive prostate cancer in men who had elevated PSA levels and a negative biopsy at baseline.

“Our purpose was to examine the effects of anti-inflammatory medication use on prostate cancer diagnosis in a study where biopsies were performed largely independent of PSA screening, because anti-inflammatory drugs can lower PSA levels and thus could cloud the real effects of these drugs on prostate cancer detection,” Adriana Vidal, PhD, assistant professor of surgery in the Division of Urology at Duke University School of Medicine, said in a statement.

“Our data support the hypothesis that anti-inflammatory drugs may have a biological role in arresting prostate cancer development, but this requires formal prospective testing in randomized trials.”

“Further, we found that NSAIDs only lower PSA by a small amount, and we predict this would have no effect on PSA’s ability to predict prostate cancer in these men,” added Vidal.

Participants were from the REDUCE study, which tested if dutasteride reduces the risk of incident prostate cancer. All men had a PSA between 2.5 ng/mL and 10 ng/mL, and a biopsy with negative results for prostate cancer prior to the start of the study.

Of the 6390 men, 50% never used aspirin and/or other NSAIDs, 21% were aspirin users, 18% were users of other NSAIDs, and 11% used both aspirin and other NSAIDs.

The researchers found that aspirin and/or NSAIDs use lowered the risk for prostate cancer by 14%. After adjusting for confounding factors, the researchers found that the use of aspirin and/or other NSAIDs reduced the risk for overall prostate cancer by 13% and the risk of high-grade prostate cancer by 17%, but no association was found with low-grade prostate cancer alone.