Regular Aspirin Use Curbs Risk of Liver and Ovarian Cancer

Roxanne Nelson, BSN, RN

October 04, 2018

Two new studies have found that regular long-term aspirin use may lower the risk of certain cancers, adding to the growing evidence that aspirin may play a role as a chemopreventive agent.

In the first study, a pooled analysis of two prospective US cohort studies, found that aspirin use was associated with a dose-dependent reduction in the risk of hepatocellular cancer (HCC), an effect that was not observed with nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs).

The second study analyzed NSAID use and ovarian cancer diagnosis using data from two large prospective cohorts and found that regular aspirin users had a lower risk of ovarian cancer. Conversely, an increased risk of ovarian cancer was observed with long-term high-quantity use of other analgesics, particularly nonaspirin NSAIDs.

In an accompanying editorial, Victoria L. Seewaldt, MD, from the City of Hope Comprehensive Cancer Center, Duarte, California, states that these two studies "have the power to start to change clinical practice."

"Both ovarian cancer and HCC are deadly cancers in need of new prevention strategies," she writes. "The findings from these two studies provide important information that can guide chemoprevention."

The two articles and editorial were published online October 4 in JAMA Oncology.

Finding the Connection

A growing number of studies have attempted to tease out the relationship between aspirin use and its possible use for chemoprevention.

Last year, for example, a large observational study found that regular aspirin use was associated with both a reduced relative risk for death from any cause and also death from cancer.

Also in 2017, a study showed that regular use of NSAIDs in long-term survivors of colorectal cancer was significantly associated with improved overall survival, although this benefit was limited to patients with KRAS wild-type tumors.

A third recent study also found that regular aspirin use was associated with a 46% reduced relative risk for pancreatic cancer.

"Several decades of research provide strong evidence that the anti-inflammatory properties of aspirin may reduce cancer risk, particularly for colorectal cancer," writes Seewaldt in her editorial. "In 2015, given the strength of the association between aspirin use and colorectal cancer risk reduction, the US Preventive Services Task Force (USPSTF) recommended that in individuals aged between 50 and 69 years with specific cardiovascular risk profiles, colorectal cancer prevention be included in the rationale for regular aspirin prophylaxis."

However, she emphasized that despite the USPSTF recommendations, there are still many unanswered questions regarding the use of aspirin as a means of lowering the risk of colorectal cancer. These include the dose and timing of aspirin chemoprevention and the molecular mechanisms underlying aspirin's chemoprevention effects.

Seewaldt says the most important unanswered question is "the ability of aspirin to prevent other malignant neoplasms."

The findings of these two new studies may help answer that last question. The articles provide "key evidence that supports the ability of regular aspirin use to prevent ovarian cancer and HCC, respectively," she says. "The findings from these two studies provide important information that can guide chemoprevention."

Reducing HCC Risk

In the first study, Tracey G. Simon, MD, from Massachusetts General Hospital in Boston, and colleagues, assessed the potential benefits of aspirin use for the primary prevention of HCC using data from the Nurses' Health Study and Health Professionals Follow-up Study, with a total cohort of 133,371 healthcare professionals (87,507 women and 45,864 men). Regular use was defined as standard dose (325 mg) aspirin tablets taken at least two or more times per week.

After more than 26 years of follow-up, the authors found that regular aspirin use was associated with a significant 49% reduced risk of developing HCC.

The HCC incidence rate among regular aspirin users was 2.1 cases/100,000 person-years, while it was 5.2 cases/100,000 person-years for non-users (P < .001). This benefit appeared to be both dose- and duration-dependent and was evident with aspirin use of 5 years or more, at a dose of 1.5 or more standard tablets per week.

Adjusting for regular use of nonaspirin NSAIDs (≥ 2 tablets/week) had no effects on the results, and the benefit from aspirin in relation to HCC was consistent across all prespecified groups (all P > .05).

As for nonaspirin NSAIDs, a reduction in HCC risk was not observed with regular versus nonregular use, and there was also no association between increasing duration of NSAID use and HCC risk (HR for ≥ 10 years of use vs nonuse, 1.06; P for linear trend = .20 among users).

"Our findings add to the growing literature suggesting that the chemopreventive effects of aspirin may extend beyond colorectal cancer," the authors conclude.

Risk Reduction in Ovarian Cancer

The second study evaluated whether regular aspirin or nonaspirin NSAID use could lower the risk of  ovarian cancer. Led by Mollie E. Barnard, ScD, from the Chan School of Public Health at Harvard University, Boston, Massachusetts, the authors evaluated the use of aspirin or nonaspirin NSAIDS with the risk of ovarian cancer.

Their data came from two prospective cohorts: 93,664 women in the Nurses' Health Study followed from 1980 to 2014 and 111,834 women in the Nurses' Health Study II followed from 1989 to 2015.

The timing, duration, frequency, and number of tablets used were evaluated for each type of analgesic (aspirin, low-dose aspirin, nonaspirin NSAIDs, and acetaminophen) and data were updated every 2 to 4 years. A total of 1054 cases of incident epithelial ovarian cancer occurred in the total combined cohort.

There were no significant associations observed between aspirin use and ovarian cancer risk when current versus nonusers were compared, regardless of dose (HR, 0.99; 95% CI, 0.83 - 1.19). But when the authors evaluated low dose and standard dose separately, there was an inverse association for low-dose aspirin (HR, 0.77; 95% CI, 0.61 - 0.96), but none for standard-dose aspirin (HR, 1.17; 95% CI, 0.92 - 1.49).

Overall, this extrapolated to a 23% lower risk of ovarian cancer among current low-dose aspirin users compared with nonusers.

There was a positive association for longer duration of use with standard-dose aspirin (≥ 5 years vs < 1 year) (HR, 1.77; 95% CI, 1.13 - 2.77; P = .004 for trend) and for 2500 or more tablet-days of standard-dose aspirin compared with no regular use (HR, 1.58; 95% CI, 1.00 - 2.48; P = .02 for trend).

In contrast, current use of nonaspirin NSAIDs was positively associated with an increased risk of ovarian cancer compared with nonuse (HR, 1.19; 95% CI, 1.00 - 1.41), with significant positive trends for duration of use (P = .02 for trend) and cumulative average tablets per week (P = .03 for trend).

These data translated into a 19% higher relative risk of ovarian cancer among regular NSAID uses compared with nonusers.

The HCC study was supported by grants from the Nurses' Health Study, Health Professionals Follow-up Study, and National Institutes of Health. The ovarian cancer study was supported by the National Institutes of Health. A co-author of the HCC study previously served as a consultant for Bayer Pharma AG on work unrelated to the study. No other disclosures were reported. Seewaldt is supported by grants from the National Cancer Institute and Prevent Cancer Foundation.

JAMA Oncol. Published online October 4, 2018. Study 1, Study 2, Editorial

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