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Study: Daily high-dose aspirin taken for at least 2 years reduces the risk of colorectal cancer but not other cancers in people with Lynch syndrome

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Contents

At a glance Clinical trials 
Study findings Guidelines
What does this mean for me? Questions for your doctor
In-depth Resources

 

STUDY AT A GLANCE

What is this study about?

This study is about whether taking daily aspirin reduces the risk of colon and other cancers in people with .

 

Why is this study important?

About one in 275 people have . is caused by an inherited mutation in one of the , , , or genes. People with have an increased risk of colorectal, endometrial and other cancers. 

People with benefit from frequent colonoscopies to detect and remove precancerous polyps. While frequent colonoscopies help find precancerous polys early, some polyps may be missed. The goal of this study was to determine whether taking daily aspirin reduced colorectal and other cancers (endometrial, stomach, ovarian) in people with .

 

Study findings

The CaPP2 (Cancer Prevention Program 2) study began in 1999. It is the first large study to look at the use of aspirin to prevent cancer in people with . The study included 861 participants with —427 participants took 600 milligrams of aspirin daily and 434 took a sugar pill daily () for up to four years. (Over-the-counter aspirin usually has 325 mg in each pill.)

Cancer outcomes (whether the participants developed cancer and what type of cancer) were analyzed at an average of 2.5 years, 4.5 years and 10 years after treatment.

  • At an average of 2.5 years, no difference was observed in cancer outcomes between those who took aspirin compared to those who took a .
  • At an average of 4.5 years, there was a significant difference in cancer outcomes between those who took aspirin compared to those who took a .
    • 18 (4.2%) of individuals in the aspirin group developed colorectal cancer compared to 30 (7%) in the group.
    • 16 (3.7%) of individuals in the aspirin group developed other (non-colorectal) cancers compared to 24 (5.5%) in the group.
       
At 4.5 years Aspirin (n=427) (n=434) Total (n=861)

Colorectal cancers

18 (4.2%)

30 (7%)

48 (5.5%)

Other Lynch cancers

16 (3.7%)

24 (5.5%)

40 (4.6%)

 

  • When all participants reached their 10-year follow-up (some reached 20-year follow-up) researchers again found that those who took aspirin had reduced risk of colon cancer:
    • 40 (9%) individuals in the aspirin group developed colorectal cancer compared to 58 (13%) individuals in the group.
  • However, no protection for other cancers was seen.
    • 36 (8.3%) individuals in the group and 36 (8.5%) in the aspirin group developed other (non-colorectal) cancers.
      • 17 women in the group developed endometrial cancer compared to 7 in the aspirin group but this was not statistically significant. The study suggested that aspirin may have a protective effect for endometrial cancer, however, this was not conclusive.

 

At 10 years Aspirin (n=427) (n=434) Total (n=861)

Colorectal cancers

40 (9%)

58 (13%)

98 (11%)

Other Lynch cancers

36 (8.3%)

36 (8.5%)

72 (8%)

 

This long-term study showed that aspirin reduced the risk of colorectal cancer for people with , although this benefit is likely delayed for a few years. The protective effect of aspirin, taken regularly for 2 years, on colorectal cancer diagnosis takes at least 4 years to become apparent. Aspirin appears to offer ongoing protection for up to 20 years. 

While aspirin reduces the long-term risk of colon cancer, it does not appear to offer long-term risk reduction for other (non-colorectal) cancers.

 

Strengths and limitations

Strengths:

  • This was a large study with long-term follow-up of participants.
  • The long-term follow-up supports that aspirin likely decreases the risk of colorectal cancer.

Limitations:

  • This was an international study, which made it difficult to collect frequent colonoscopy data on all participants.
  • Aspirin is a widely available, over-the-counter medication. Participants may have chosen to continue aspirin (or take aspirin, in the case of people in the arm) without the knowledge of the study researchers. This was not reported.
  • This study had participants taking aspirin for two years. A longer period of aspirin use may show different results.
  • Future studies are needed to identify the best dose of aspirin and how long it should be taken to provide the highest level of risk reduction for colorectal cancer among patients with .
  • The age of the patients were relatively young (45 years on average). Older patients may have different side effects (example, stomach ulcers and gastrointestinal bleeding).

 

What does this mean for me?

Results of this study suggest that aspirin may reduce the risk of colon cancer for patients with . However, the dose and required length of use remain to be determined. The Cancer Prevention Project 3 (CaPP3) will compare three different doses of aspirin to find which is the best for reducing cancer risk in people with

It is important to understand that the benefit of aspirin may not be apparent for several years after treatment. However, the benefit may last for up to 20 years. When the benefit of taking a drug persists for years after the drug is stopped, this is referred to as a “legacy effect.”

If you have , it is important for you and your doctor to discuss specific measures you can take to reduce your cancer risk. In some people, aspirin may cause stomach irritation and have other health impacts. You may want to discuss the risks and benefits of daily aspirin with your doctor.

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posted 5/17/21


References

Burn J, Sheth H, Elliott F, Reed L, et al. Cancer prevention with aspirin in hereditary colorectal cancer (), 10-year follow-up and registry-based 20-year data in the CAPP2 study: a double-blind, , trial. Lancet. 2020 Jun 13;395(10240):1855-1863.

Burn J, Gerdes AM, Macrae F, et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 . Lancet. 2011 Dec 17;378(9809):2081-7.

Burn J, Bishop DT, Mecklin JP, et al. Effect of aspirin or resistant starch on colorectal neoplasia in the . New England Journal of Medicine. 2008 Dec 11;359(24):2567-78.


Disclosure

FORCE receives funding from industry sponsors, including companies that manufacture cancer drugs, tests and devices. All XRAYS articles are written independently of any sponsor and are reviewed by members of our Scientific Advisory Board prior to publication to assure scientific integrity.

This article is relevant for:

People with Lynch syndrome

This article is also relevant for:

People with a family history of cancer

People with a genetic mutation linked to cancer risk

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IN-DEPTH REVIEW OF RESEARCH

 

Study background

is a syndrome that is caused by an inherited mutation in one of five genes: , , , or .  People with are at increased risk of colon and other cancers, especially endometrial cancer.

Many studies have consistently shown a link between daily aspirin use and reduced cancer risk, especially the risk for colorectal cancer. In fact, the United States Preventive Services Task Force recommends daily low-dose aspirin to help prevent colorectal cancer in adults who are age 50 to 59 years with a 10% or greater risk of cardiovascular disease in 10 years.

Daily aspirin use has also been linked to reduced colorectal and ovarian cancers in some people who do not have (see our XRAY review). While daily aspirin use has been studied as a preventive measure against the onset of cancers such as , ovarian, endometrial, and breast cancers, the findings do not consistently show that aspirin protects against these cancer types.

The CAPP2 trial was the first large-scale trial involving patients with to test a drug that may reduce cancer risk. Participants were randomly assigned to receive 600 mg/day of aspirin or a for at least two years (some took aspirin for up to 4 years, the average participant to aspirin for 25 months). Two years after participants stopped taking aspirin or , no significant difference was found in the rate of colorectal cancer between the two groups. When the first participants reached their 10-year follow-up, the researchers found that those who were assigned to the aspirin group had significantly fewer colon and other Lynch syndrome-related cancers.

The results presented here reflect the 10-year follow-up milestone for all participants, and some patients reached a 20-year follow-up.

 

Researchers of this study wanted to know:

Researchers wanted to know whether daily aspirin can be used to reduce cancer risk among patients with . This latest analysis allowed researchers to test the long-term effects of taking regular aspirin among patients in this population.

 

Populations looked at in this study:

All participants had .  At the time of enrollment, the mean age of participants was 45 years. Most participants were from Europe (82%), while others were from Australia (13%) and Africa (4%); less than one percent were from the Americas.

 

Study design:

Between January 1999 and March 2005, 861 participants were randomly assigned to the aspirin group or the group. The aspirin group consisted of 427 participants who received 600 mg of aspirin daily for two years while the group consisted of 434 participants who received a sugar pill daily for two years. Researchers monitored for at least 10 years whether participants were diagnosed with cancer; some participants were monitored through national registries of some countries for up to 20 years.

 

Study findings:

  • When the first participants reached their 10-year follow-up researchers found that those who took aspirin had substantial protection against colorectal cancer and other cancers. (The average follow-up time for all the participants at this time was almost 5 years.)
    • 30 (7%) people in the group developed colorectal cancer compared to 18 (4.2%) people in the aspirin group.
    • 24 (5.5%) people in the group developed other (non-colorectal) cancers compared to 16 (3.7%) people in the aspirin group. Of these:
      • 13 women in the group developed endometrial cancer compared to 5 in the aspirin group.
  • When all participants reached their 10-year follow-up researchers found that those who took aspirin had substantial protection against colorectal cancer, confirming their earlier results.
    • 58 (13%) people in the group developed colorectal cancer compared to 40 (9%) people in the aspirin group.
    • While earlier results showed protection by aspirin for some non-colorectal cancers this finding was not statistically significant in the final analysis.
      • 36 (8.3%) people in the group and 36 (8.5%) people in the aspirin group developed other (non-colorectal) cancers. Of these:
        • 17 women in the group developed endometrial cancer compared to 7 women in the aspirin group but this was not statistically significant.

patients who took a daily aspirin for up to four years had fewer cases of colorectal cancer. 
 

Strengths and Limitations

 

Strengths:

  • This was a large study with long-term follow-up of participants.
  • The long-term follow-up supports that aspirin likely decreases the risk of colorectal cancer.

 

Limitations:

  • This was an international study, which made it difficult to collect frequent colonoscopy data on all participants.
  • Aspirin is a widely available, over-the-counter medication. Participants may have chosen to continue aspirin (or take aspirin, in the case of people in the arm) without the knowledge of the study researchers. This was not reported.
  • This study had participants taking aspirin for two years. A longer period of aspirin use may show different results.
  • Future studies are needed to identify the best dose of aspirin and how long it should be taken to provide the highest level of risk reduction for colorectal cancer among patients with .
  • The age of the patients were relatively young (45 years on average). Older patients may have different side effects (example, stomach ulcers and gastrointestinal bleeding).
  • The researchers were not able to comment on how aspirin affects mortality in patients with . This requires a much larger study.
  • The specific gene mutations of the participants were not known. It is also unknown whether people with certain gene mutations had different outcomes than all patients combined.
  • Because study participants were mostly Caucasian, these results may not apply to other racial groups.

 

Context

In 1998 researchers of a colorectal case-control study reported that aspirin may have a protective effect. Since then, over 100 studies have confirmed that aspirin can reduce cancer risk. The large Women’s Health Study (WHS) showed no effect of aspirin on cancer at 10 years but concluded that at 18 years participants who were randomly assigned to receive aspirin had significantly lower rates of colon cancer.

The CAPP2 study results are similar. It also showed that the preventive effect of aspirin, particularly on the risk of colon cancer, is delayed and continues for up to 10 years in patients with . The ongoing Cancer Prevention Project 3 (CaPP3) trial will compare three different doses of aspirin to find the dose that most effectively reduces cancer risk in people with

While aspirin has been linked to reduced risk of cancers, such as breast, and colorectal cancers, the evidence for a similar reduction of endometrial cancer risk is conflicting. Whether an association exists remains unclear. A recent of the literature suggests that aspirin is associated with a reduced risk of endometrial cancer, and the reduced risk is closely linked to the frequency of use. Further controlled trials are needed to confirm these findings.

 

Conclusions

The results of the CAPP2 study support the recommendation that adults with take up to 600 mg of aspirin daily for at least two years to reduce their risk of colorectal cancer. It is important to understand that the benefit of aspirin may not be apparent for several years after treatment. This is called a legacy effect.

While it is currently unknown exactly how aspirin works to prevent cancer, these results support other studies that indicate the benefit of aspirin in cancer prevention. You can see our review of another study of how cancer risk factors such as obesity, smoking, physical inactivity or a family history of cancer can modify the risk-reducing benefits of daily aspirin here.

Share your thoughts on this XRAYS article by taking our brief survey.
posted 5/17/21

Expert Guidelines
Expert Guidelines

The National Comprehensive Cancer Network (NCCN) provides risk management guidelines for people with  mutations.

Colorectal cancer 

  • Colonoscopy every 1-2 years. Speak with your doctor about whether your screenings should be yearly or every two years. Men, people over age 40, and people with a personal history of colon cancer or colon polyps may benefit most from yearly screenings. 
    • For people with , or EPCAM:
      • beginning between ages 20-25 (or 2-5 years before the earliest age of colon cancer in the family, if diagnosed before age 25).
    • For people with or PMS2: 
      • beginning between the ages of 30-35 (or 2-5 years before the earliest age of colon cancer in the family, if diagnosed before age 35).
  • Daily aspirin can decrease the risk for colorectal cancer. The best dose and timing for aspirin is not known. Speak with your doctor about the benefits and risks, best timing and dose.

Endometrial and ovarian cancer

  • Be aware of endometrial and ovarian cancer symptoms.
  • Consider endometrial biopsy every 1-2 years beginning at age 30-35.
  • Discuss the benefits and risks of oral contraceptives.
  • Consider risk-reducing hysterectomy; discuss risk-reducing removal of ovaries and with your doctor (, , and ).

Other cancers

  • Consider annual cancer screening with testing and digital rectal exam.
  • For people with a family history of urethelial cancer and men with an mutation:
    • Consider annual urinalysis beginning at age 30-35.
  • Consider baseline esophagogastroduodenoscopy with random stomach biopsy at age 40. 
    • consider continuing this surveillance every 3-5 years for people in a high risk catgory for gastric cancer. 
  • Consider testing for H. pylori and treating if positive. 
  • For people with a family history of pancreatic cancer:
    • Consider annual cholangiopancreatography (MRCP) and/or endoscopic (EUS) beginning at age 5-. 
    • Consider participating in a pancreatic cancer screening study. 
  • Consider annual physical and neurological exam. 

Updated: 12/22/2021

Questions To Ask Your Doctor
Questions To Ask Your Doctor

  • Should I take a daily aspirin to reduce my colon cancer risk?
  • What are the benefits and risks of taking a daily aspirin to reduce my colon cancer risk?
  • What dose and for how long should I take a daily aspirin to reduce my colon cancer risk?
  • What other ways can I reduce my risk of Lynch syndrome-associated cancers?

Open Clinical Trials
Open Clinical Trials

The following screening and prevention studies are open to people with

Colorectal cancer

Gynecologic cancers

 cancer

  • NCT03805919: Men at High Genetic Risk for  Cancer. This is a  cancer screening study using  in high risk men. This study is open to men with  and other mutations.
  • NCT05129605: Cancer Genetic Risk Evaluation and Screening Study (PROGRESS).  This study will look at how well  MRI works as a screening tool for men at high risk for cancer. This study is open to men with inherited mutations in , , , , , , HOXB13, , , , , , , , , and other genes. 

Pancreatic cancer

  • NCT02206360: Pancreatic Cancer Early Detection Program. This pancreatic cancer screening study uses esopheal  to screen for pancreatic cancer in high risk people. The study is open to people with a  mutation or other mutation linked to increased cancer risk who also have a family history of pancreatic cancer.
  • NCT03568630: Blood Markers of Early Pancreas Cancer.  This pancreatic cancer study involves blood samples over time to look for biomarkers of pancreatic cancer in high risk people. The study is open to people with an  mutation or other mutation linked to increased cancer risk.
  • NCT03250078: A Pancreatic Cancer Screening Study in Hereditary High Risk Individuals. The main goal of this study is to screen and detect pancreatic cancer and precursor lesions in individuals with a strong family history or genetic predisposition to pancreatic cancer.  and Magnetic cholangiopancreatography (MRI/MRCP) will be utilized to screen for early  pancreatic lesions.

A number of other clinical trials for patients with endometrial cancer can be found here.

Updated: 09/19/2022

Peer Support
Peer Support

FORCE offers many peer support programs for people with inherited mutations. 

Updated: 08/06/2022

Who covered this study?

Medical dialogues

Aspirin use linked to lower bowl cancer risk This article rates 4.0 out of 5 stars

The Sydney Morning Hearld

An aspirin a day helps keep bowel cancer away, study finds This article rates 4.5 out of 5 stars

Science Daily

An aspirin a day keeps the bowel doctor away This article rates 4.5 out of 5 stars

How we rated the media

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