ACS Research Highlights

More Evidence: Daily Aspirin May Help Prevent Colorectal Cancer

With data from 52 studies, including ACS CPS-II, scientists found 2 genetic markers that interact with aspirin/NSAIDs to reduce colorectal cancer risk.

The Challenge

Nonsteroidal anti-inflammatory drugs (NSAIDs) are a class of medicines that reduce pain, inflammation, and fever. Several types of NSAIDs are available over-the-counter, including aspirin, ibuprofen (with brand names including Advil and Motrin), and naproxen (with brand names including Aleve).

Large research studies have shown that regular, long-term use of aspirin helps reduce the risk of developing colorectal cancer by about 20% to 30%. The exact mechanism of action is not fully known.  

Not all studies differentiate between the use of aspirin and other NSAIDs or describe the reasons people take NSAIDs. Those factors may be part of the reason studies about the relationship between non-aspirin-NSAIDs and the risk of developing colorectal cancer have been less consistent. 

Scientists think genetic variants/markers in people are likely the factor that interacts with aspirin and NSAIDs to determine whether these drugs affect the risk of developing colorectal cancer. The most common type of variant in the human genome are single nucleotide polymorphisms (SNPs). SNPs can act as biological markers to help scientists locate the specific genes associated with a specific disease.

The Research

A recent study in Science Advances aimed to clarify whether aspirin and/or other NSAIDs influence the risk of developing colorectal cancer and also to identify the specific genetic markers involved.

The researchers conducted a genome-wide interaction scan (GWIS) to detect gene-drug interactions. They wanted to identify which SNPs are related to the regular use of aspirin and/or other NSAIDs. They also wanted to know whether that interaction between aspirin/NSAIDs and genetic markers could reduce the risk of developing colorectal cancer. 

This is the largest genome-wide gene-drug interaction study completed so far that is focused on aspirin and NSAID use in people with colorectal cancer. A review of data from more than 72,500 people showed that regular use of aspirin alone and/or other NSAIDs, reduces the risk of developing colorectal cancer. Our research group was also the first to identify 2 genetic regions that modify that protective effect."

Anita Peoples, PhD, MPH

Senior Principal Scientist, Cancer Survivorship and Epidemiology Research

Population Science, American Cancer Society

Compared to previous, similar studies, the team of over 70 researchers used a much larger study group, combining data from 52 studies—more than 72,500 people who had reported whether or not they used aspirin and/or other NSAIDs. The population group was divided between cases (people with colorectal cancer) and controls (people without colorectal cancer).

The researchers for this large study also powered up their use of statistical methods to improve the ability to detect specific locations on a gene and improve the ability to understand the results of the interaction.

Compared to people without cancer/in the control group, the group with colorectal cancer tended to:

  • Be older
  • Have less education
  • Have a higher body mass index (BMI) and eat more
  • Be more likely to have a history of risk factors related to lifestyle, including heavy alcohol use and/or tobacco smoking
  • Be more likely to have a family history of colorectal cancer
  • Be less likely to have regularly used either aspirin alone and/or other types of NSAIDs

What they learned from the gene-drug interaction scan:

Reduced risk regardless of healthy or unhealthy lifestyles. Regular use of aspirin and/or other NSAIDs reduces the risk of developing colorectal cancer, even after accounting for other established colorectal cancer risk factors, such as having a high BMI, smoking, and having a diet that includes too much alcohol and/or too much red meat.

Women had greatest response. The relationship between using an NSAID (except for aspirin alone) and a reduced risk of colorectal cancer was stronger among women than men.

Two new markers. The researcher identified two interaction SNPs not previously described: rs350047 (5p12.1) and rs72833769 (6p24.1).

Location matters. There were effects of different magnitudes for aspirin/NSAIDs on colorectal cancer based on the physical location of the region of the gene (called the locus). The research team determined that rs350047 had a significant interaction with aspirin's preventive capacity, and that it was both "biologically plausible" and "potentially functionally relevant." They found rs72833769 to be biologically plausible and the functional evidence to be less clear.

Several American Cancer Society (ACS) researchers participated in this study: Christina Newton, MSPH; Anita Peoples, PhD, MPH, and Caroline Um, PhD, MPH, RD. Data from the ACS Cancer Prevention Study-II was part of the data pool. Andrew T. Chan, MD, MPH, with Massachusetts General Hospital in Boston and an ACS Professor was one of the senior authors of the study. Dr. Chan is an expert in the field of colorectal cancer prevention with NSAIDs.

Why It Matters

The results of this study add to the existing evidence that genetic markers can predict aspirin’s preventive effect for colorectal cancer. More specifically, the researchers found that the preventive effect was a result of aspirin/NSAIDs acting synergistically with specific genetic variants, such as SNPs.  

Their identification of genetic variants is an early step toward a future with more precise prevention approaches. The more genetic subsets of people that can be identified, the better scientists will be able to predict who’s most likely to benefit from the preventive aspect of aspirin/NSAIDs for colorectal cancer, as well as those who won’t. 

This analysis is limited to individuals of European ancestry, so future studies will need to take other ethnicities and races into account.