Aspirin, or acetylsalicylic acid, is a nonsteroidal anti-inflammatory drug (NSAID) that irreversibly inhibits both COX-1 and COX-2, thus resulting in its anti-inflammatory, analgesic, and antipyretic properties.1 In addition to an over-the-counter analgesic, aspirin is also used as a treatment for acute coronary syndrome and for secondary prevention of atherothrombotic complications.2

It has also been hypothesized that aspirin has anticancer effects. This was originally based on epidemiologic data that suggested that aspirin use can reduce the risk of colorectal cancer (CRC).2 The United States Preventive Services Task Force (USPSTF) indicates that low-dose aspirin can be used for the primary prevention of CRC in select adults aged 50 to 59 years.

Studies also suggest that aspirin use may reduce the risk of other cancers.3 A meta-analysis of 218 studies found that aspirin use significantly decreased the risk of overall cancer (relative risk [RR], 0.89; 95% CI, 0.87-0.91) and, more specifically, reduced the risk of gastrointestinal tract cancers, and male and female reproductive tract cancers.

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This fact sheet will focus on the potential association between aspirin use and the risk of hepatocellular carcinoma (HCC) and ovarian cancer. Though many studies suggest an inverse association, the data remain mixed.

Liver Cancer

Most studies suggest that aspirin use decreased the risk of HCC and may improve outcomes among patients with HCC. In a meta-analysis, analysis of 5 studies demonstrated that aspirin use significantly decreased the risk of HCC by 36% (hazard ratio [HR], 0.64; 95% CI, 0.45-0.91), but not NSAIDs overall nor nonaspirin NSAIDs.4 In contrast, another meta-analysis found that aspirin had no effect on HCC risk, but nonaspirin NSAIDS decreased the risk of HCC (HR, 0.81; 95% CI, 0.70-0.94).5 These meta-analyses included some different studies, which may be the reason for the divergent results. Also, the differences between the included studies, such as study design and aspirin dose, may have introduced bias, which could skew the results.

A large US-based cohort study of 133,371 individuals with a median follow-up time of 26 years demonstrated that regular aspirin use — defined as at least 2 standard dose (325 mg) tablets per week) — significantly reduced the risk of HCC by nearly 50% compared with nonuse (HR, 0.51; 95% CI, 0.34-0.77).6 There was a dose-response relationship; increasing the number of tablets per week or the duration of therapy further lowered the risk. There was no association between nonaspirin NSAID use and incidence of HCC. Aspirin use also decreased the risk of HCC in a Korean population, 7% of whom had viral hepatitis.7 This cohort study of 460,775 individuals found that aspirin use reduced the risk of HCC compared with nonuse (HR, 0.87; 95% CI, 0.77-0.98), also with a dose-dependent relationship.

Among patients with HCC, a meta-analysis of 2 studies found that aspirin use significantly decreased mortality at 2 (RR, 0.50; 95% CI, 0.36-0.69) and 4 (RR, 0.67; 95% CI, 0.45-0.998) years. There was no increased risk of bleeding associated with aspirin use.