Aspirin, colon cancer, and genetics

Colon cancer risk factors include environmental exposure (diet, toxicants, etc.) as well as genetic variants that increase or decrease your susceptibility. When it comes to preventing colon cancer, doctors often recommend dietary changes, and your doctor may also mention that studies show that taking aspirin regularly also decreases the risk of colon cancer.  Personalization is the key here, though, because that protection from aspirin may only be for people with certain genetic variants.

Should you take aspirin to prevent colon cancer?

Colon cancer is one of the most common forms of cancer, with a lifetime risk of about 5%. The good news is that survival rates are high for those who detect it early. At later stages, though, the mortality risk is high for metastasized colon cancer.[ref]

Aspirin is dirt cheap and has been used for a hundred-plus years. Recently, it has been in the news as possibly preventing several types of cancer, including colon cancer.

The jury is still out, though, on whether or not to recommend aspirin to everyone as a way to prevent cancer.  The American Cancer Society currently only recommends taking low-dose aspirin for colon cancer prevention if you also would benefit from it for heart disease prevention. [ref]

What are the risks of taking aspirin for cancer prevention?

Aspirin is a blood thinner, so frequent use includes bleeding risks. This risk may be a significant detriment for older people who are at a higher risk of colon cancer due to age. For younger people, the risk of gastric bleed each year is 1 or 2 in a thousand, but this increases to around 7 in 1000 for people over the age of 80.[ref] If you are concerned about the risk of bleeding, you should talk with your doctor and weigh the benefits vs. the risk.

Using genetics to determine the value of aspirin for colon cancer:

It turns out that genetic variants play a significant role in whether aspirin reduces the risk of colon cancer for an individual.

How exactly does aspirin affect colon cancer?  

The cyclooxygenase enzymes (COX-1 and COX-2) are involved in inflammatory responses. Inflammation is an important part of the body’s immune response to trauma or pathogens. Problems arise, though, when the inflammatory process doesn’t turn off when it is supposed to.

COX inhibitors decrease inflammation and thus the pain associated with it. Aspirin is a COX inhibitor, along with NSAID pain relievers such as ibuprofen. Other natural COX inhibitors include Vitamin D, St. John’s Wort, and fish oil.[ref]

Research shows that COX-1 is usually associated with acute inflammation – the inflammation that occurs with trauma and pathogens. COX-2 is linked to maintaining that inflammatory response.[ref]

Inhibiting COX-2 alone has been shown in studies to reduce colon cancer. [ref]

While inhibiting COX-2 may reduce colon cancer, research shows that you don’t want to block COX-2 without also inhibiting COX-1. Drugs that inhibit only COX-2, such as Vioxx, have been found to increase the risk of cardiovascular events.  (Vioxx was taken off the market in 2004 due to a significant increase in the risk of heart attacks and strokes.) [ref]

Aspirin and other NSAIDs inhibit both COX-1 and COX-2. Studies dating back to the mid-90s have shown that low-dose NSAID use for the prevention of heart disease also decreases the risk of colon cancer. The benefit ranges from a 21% decrease in risk to a 31% decrease in risk for regular aspirin or other NSAID users.[ref][ref][ref]

While research is still ongoing, there are at least two ways that aspirin and other NSAIDs reduce colon cancer risk:

  • Aspirin may reduce the ability of cancer cells to proliferate through the anti-platelet pathway. This could help to reduce the activation of the oncogene c-MYC.[ref][ref]
  • Some cancer tumors express increased levels of COX-2. For example, animal studies show that decreasing COX-2 genetically can decrease tumors formed in epithelial cells. Additional research indicates that COX2 inhibition in prostate cancer cells decreases proliferation.[ref][ref]

Genetic Variants:

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Research shows that variants in genes related to COX2 signaling and colon cancer risk interact with aspirin usage when it comes to colon cancer prevention.

CCAT2 gene:

The CCAT2 gene codes for a long non-coding RNA that is important in colon cancer prevention.  According to a 2013 study, those with the T allele benefitted from aspirin in the prevention of colon cancer.  Those with a T allele who were taking two or more regular aspirin in a week had their risk cut by 40 – 50%. [ref]  The T allele also reduces the overall risk of colon cancer [ref]

Check your genetic data for rs6983267 (23andMe v.4, v.5; AncestryDNA):

  • T/T: reduced risk of colon cancer, even greater reduction in risk with regular aspirin use[ref]
  • G/T: reduced risk of colon cancer, even greater reduction in risk with regular aspirin use
  • G/G: typical; no reduced risk of colon cancer with aspirin

Members: Your genotype for rs6983267 is .

 

TCFL2 gene:

The TCFL2 gene codes for transcription factor 7-like 2 (TCF7L2). Variants in the gene have been associated with insulin sensitivity and the risk of diabetes. The gene is also involved in the Wnt/β-catenin signaling pathway, which affects colon cancer risk. [ref]

Check your genetic data for rs7903146  (23andMe v.4, v.5; AncestryDNA):

  • T/T: reduction in risk of colon cancer with regular aspirin use[ref]
  • C/T: some reduction in risk of colon cancer with regular aspirin use
  • C/C: no reduced risk of colon cancer with aspirin

Members: Your genotype for rs7903146 is .

 

SMAD7 gene:

The SMAD7 gene codes for a protein involved in inflammation-related pathways. A genome-wide association study found that variants in SMAD7 were important in colon cancer risk, and a follow-up study found that aspirin or NSAID usage also interacts with these variants. [ref]

Check your genetic data for rs4939827 (23andMe v4, v5; AncestryDNA):

  • C/C: greater decrease in cancer risk with regular aspirin usage [ref]
  • C/T: typical (most common genotype in some population groups)
  • T/T: typical

Members: Your genotype for rs4939827 is .

Note: Other variants (not tested by 23andMe) also can lead to decreased colon cancer risks with aspirin, so you can’t rule anything out with this information.


Lifehacks:

Dosage and Timing:

Talk with your doctor if you have questions before starting an aspirin regimen.  

If you carry the genetic variants above that reduce the risk of colon cancer with aspirin use, it may be helpful to read and understand some of the details in the epidemiological studies. Keep in mind that there may be other genetic variants that also decrease cancer risk with aspirin usage, so you can’t rule out a benefit just from your 23andMe or AncestryDNA data.

  • The studies on NSAID use show that it is the repeated usage that decreases cancer risk. This isn’t a one-and-done type of situation. For some studies, the statistical benefit in reduced risk is seen after 6+ years. [ref][ref]
  • More isn’t always better…  Low-dose aspirin (~75 mg) taken 4+ times per week seems to be effective and is less likely to cause gastric bleeding. [ref]

 

Do other natural COX inhibitors also decrease cancer risk?

If aspirin isn’t a good fit for you, there may be benefits from other natural COX-2 inhibitors as well.

  • Cell studies show that DHA, which is found in fish oil, suppresses colon cancer cell growth.[ref]
  • Fisetin, a flavonoid found in various fruits and vegetables, has been shown in cell studies to inhibit COX-2 in colon cancer cells. Fisetin is available as a supplement.[ref]
  • Quercetin, another flavonoid, may also help reduce tumor formation through a couple of pathways including the downregulation of COX-2. [ref]

 

Originally published 8/2016; updated and revised 8/2020



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.