Aspirin in the Prevention of Colorectal Neoplasia

Abstract

High-quality evidence indicates that regular use of aspirin is effective in reducing the risk for precancerous colorectal neoplasia and colorectal cancer (CRC). This has led to US and international guidelines recommending aspirin for the primary prevention of CRC in specific populations. In this review, we summarize key questions that require addressing prior to broader adoption of aspirin-based chemoprevention, review recent evidence related to the benefits and harms of aspirin use among specific populations, and offer a rationale for precision prevention approaches. We specifically consider the mechanistic implications of evidence showing differences in aspirin's effects according to age, the potential role of modifiable mechanistic biomarkers for personalizing prevention, and emerging evidence that the gut microbiota may offer novel aspirin-associated preventive targets to reduce high-risk neoplasia.

Keywords: chemoprevention; colorectal cancer; nonsteroidal anti-inflammatory drugs; personalized medicine; precision chemoprevention.

Figure 1

A model for precision chemoprevention in clinical decision making. Physicians may consider timing a discussion of use of aspirin for primary prevention to coincide with an individual’s first screening colonoscopy (recommended between ages 45 and 50). For individuals under age 60, after consideration of cardiovascular disease (CVD) risk factors, life expectancy, and risk for bleeding events, providers may recommend aspirin directly. For individuals over age 60, providers may want to consider colorectal cancer (CRC) risk factors, including the presence of adenomas and baseline levels of potentially modifiable biomarkers for CRC risk. In this example, we use urinary prostaglandin metabolites (PGE-M) as a risk biomarker that has recently been shown to be modifiable as a potentially useful precision tool to monitor a possible aspirin chemoprotective benefit while also monitoring for potential harms; PGE-M can help tailor individual strategies according to aspirin dose, duration, and continuation of use. Precision prevention strategies may be extended to those of advanced age (70 years or older); however, significant considerations of harms is warranted before starting an aspirin prevention regimen.