Aspirin for Colorectal Cancer Prevention

Colorectal Cancer (CRC) is a highly prevalent and deadly form of cancer worldwide. In fact, it is the fourth most commonly diagnosed cancer and the third leading cause of cancer death globally. From first glance, the outlook for colorectal cancer may seem grim. However, the good news is that CRC can also be prevented through screening and lifestyle modification. Widespread implementation of screening techniques such as colonoscopy, CT, fecal occult blood testing, and fecal immunochemistry have allowed for detection and removal of early precursors of cancer known as polyps. As a result, mortality associated with CRC has been on the decline, despite its increasing incidence.

Colorectal Cancer and Inflammation

Interestingly, CRC is 3-4 times more common in developed countries than developing countries. Its prevalence is also increasing in developing countries that are beginning to adopt a more western way of life. Some of the CRC risk factors associated with the so-called western lifestyle include: 

• Increased sedentary time
• Obesity
• Sleep deprivation
• Excess red meat and processed meat consumption
• Alcohol consumption
• Use of tobacco products

The link between these lifestyle factors and CRC incidence lies in chronic inflammation. Inflammatory states can damage the intestinal epithelium, and repeated damage can predispose to the development of cancer-causing mutations over time. In addition, a highly inflammatory diet and lifestyle can lead to changes in the gut microbiome, activating an immune response. This also allows for easier growth of polyps and conversion of benign adenomas to cancerous foci.

Evidence for Long-Term Aspirin Use in CRC Prevention

Because chronic inflammation is such a key factor in the development of CRC, it follows that reducing inflammation could potentially lower the risk of developing colon cancer. Therefore, an anti-inflammatory approach that has been highly studied in the past few decades is chronic aspirin use. As a non-steroidal anti-inflammatory drug (NSAID), aspirin inhibits inflammation-related pathways that can serve as fuel for both the development and spread of colorectal cancer. According to Dr. Mona Rezapour, a gastroenterologist at UCLA Health, aspirin can have additional positive effects on the gut microbiome. More specifically, it encourages the growth of beneficial bacteria in the gut. Increased amounts of these “good bacteria” can also suppress inflammation and therefore decrease the risk of developing colorectal cancer. 

Despite mixed results of early studies regarding colorectal cancer risk and aspirin use, the positive effects of long-term aspirin have recently become backed by a strong body of scientific evidence. A key study published in JNCI in April 2024 provides the first true insight into the effects of long-term aspirin use on CRC risk. This 18-year cohort study followed patients from the late 1990s, placing them into groups based on aspirin use and assessing their rates of colorectal cancer and various other cancers.  Results showed a significant reduction in colorectal cancer risk, specifically among long-term and continuous aspirin users who had started taking aspirin before the age of 70. This population also had a reduction in liver cancer, pancreatic cancer, meningioma, and leukemia. This echoes the importance of chronic and consistent aspirin use in cancer reduction efficacy. This study is the first longitudinal assessment of the effectiveness of aspirin alone on CRC risk, as well as the risk of other cancers, and it has yielded highly promising results. 

For these reasons, aspirin has recently gained favor with the USPSTF, or U.S. Preventive Services Task Force. It is now recommended that patients who meet certain criteria take aspirin daily on a long-term basis to achieve a reduction in CRC risk of up to 40%. 

Risks of Long-Term Aspirin Use

However, following the USPSTF guidelines for aspirin use is extremely important, as long-term aspirin use is not without risks. One of the major risks associated with all NSAIDs is GI bleeding. However, risk can be minimized by following the listed guidelines and talking to your doctor about starting a long-term aspirin regimen. 

In addition, the Skriver et al. longitudinal aspirin study found that, although aspirin does reduce CRC risk, it can actually increase the risk of certain other cancers. These include lung and bladder cancers, and their risk was increased with aspirin use, regardless of dose or duration. As such, long-term aspirin use, like any other medical therapy, is not right for everyone. This further underscores the importance of consulting with a physician before starting any duration of continuous aspirin use.

Conclusion

All in all, the recently concluded cancer reduction risk in long-term, low-dose aspirin users shows promise for combatting the inflammatory etiology of CRC. Recent evidence, which has led to a change in USPSTF guidelines, shows that aspirin can significantly reduce CRC risk when used consistently over long periods of time. As aspirin is a widely available therapy, this has the potential to be highly effective reducing the incidence and mortality associated with colon cancer worldwide. If lifestyle changes are additively implemented, CRC risk reduction can be maximized, creating a revolutionary impact on global health.

Summary

The incidence of colorectal cancer has been rising in recent decades, and CRC poses a major global health threat in terms of mortality. Although screening techniques have recently improved the survival rates of the disease by catching it in its earlier stages, there is still more that can be done to combat this deadly cancer. Recent scientific evidence has shown promise for the use of long-term, low-dose aspirin in mitigating colon cancer risk. 

Aspirin targets the chronic inflammation that causes CRC and improves the gut microbiome profile, therefore reducing the risk of developing CRC at all and the risk of metastasis for existing CRC. As such, chronic low-dose aspirin therapy has recently become recommended by the USPSTF to decrease CRC development and mortality in certain patients. However, it is important to talk to a doctor before starting aspirin therapy, as there is risk of GI bleeding, along with potential for increasing bladder and lung cancer risk. Overall, implementing long-term aspirin use along with lifestyle modifications can have a profound impact in decreasing CRC incidence and mortality worldwide.