Aspirin, Risk of Colorectal Cancer, & Genetic Risk-Letter.

Abstract

We read with interest the study by Bakshi and colleagues in which they explored the association between genetic susceptibility to colorectal cancer and aspirin, using a 95-variant colorectal cancer polygenic risk score (PRS) in the participants of ASPREE (ASPirin in Reducing Events in the Elderly) trial (1). The ASPREE trial was a prospective double-blinded, placebo-controlled randomized trial in which 12,609 individuals of European descent ages ≥70 years were enrolled. They concluded that the 95-SNP PRS continues to identify individuals at higher risk of colorectal cancer, including individuals with no family history of colorectal cancer. Recently, Chen and colleagues, using data collected from a large population-based case–control study on colorectal cancer in Germany, analyzed PRS based on 140 colorectal cancer–related risk loci to quantify the genetic risk, reported that regular use of NSAIDs, including aspirin, was associated with significantly reduced colorectal cancer risk regardless of individual genetic profile (2). However, randomization of aspirin treatment in the ASPREE trial was not associated with a reduced incidence of colorectal cancer (P = 0.7).Also, a pooled analysis of two large U.S. cohort studies was published, the Nurses’ Health Study and Health Professionals Follow-up Study, with a total of 94,540 participants ages ≥70 years old (3). The analysis showed that initiating aspirin at an older age was not associated with a lower risk of colorectal cancer. In contrast, those who used aspirin before age 70 years and continued into their 70s or later had a reduced risk of colorectal cancer. A possible explanation is that a beneficial effect of aspirin for colorectal cancer requires at least 5 to 10 years of use (3).Over the last decades, aspirin has been an extensively prescribed drug with antiplatelet and anti-inflammatory effects (4). The mechanism of aspirin's possible anticancer effect is under investigation, but it is believed that it is through inhibiting catalytic enzymes COX-1 and COX-2 involved in prostaglandin synthesis. Therefore, in subjects taking aspirin, gut microbiome composition will shift toward a lower proportion of proinflammatory, colorectal cancer–predisposing bacteria (e.g., Fusobacteria) and a higher proportion of anti-inflammatory, colorectal cancer–protective bacteria (e.g., butyrate-producing bacteria; ref. 5).The recent study by Bakshi and colleagues and other recent high impacted trials on the effect of aspirin on cardiovascular disease and colorectal cancer risks have high translational values into the daily practice. However, there is a need for future preclinical and clinical trials on the impact of aspirin on gut microbiota and their metabolic and immunoregulatory potential.See the Response, p. 703No disclosures were reported.