Get notified of page updates

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

Research has shown that daily aspirin use can reduce the risk of colon and other cancers. The Cancer Prevention Program 2 (CaPP2) study looked at the effect of daily aspirin in patients with Lynch syndrome. After 10 years of follow-up, the results showed that taking daily aspirin for two years reduced the frequency of colon cancer in patients with Lynch syndrome, and importantly, did not result in an increase in side-effects or complications. No benefit was seen for other Lynch syndrome-related cancers, including endometrial cancer. (5/17/21)

Este artículo está disponible en español.

Read the Original Article PRINTER FRIENDLY PAGE

Glossary on

off

Most relevant for: People with Lynch syndrome.

It may also be relevant for:

people with a family history of cancer
people with a genetic mutation linked to cancer risk

Relevance: High

Strength of Science: High

Research Timeline: Post Approval

Relevance rating details

Did you see the media coverage of this article?

See all media ratings.

How we rated the media

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

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 Lynch syndrome. Lynch syndrome is caused by an in one of the , , , or genes. People with Lynch syndrome have an increased risk of colorectal, endometrial and other cancers.

People with Lynch syndrome benefit from frequent colonoscopies to detect and remove precancerous . 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 Lynch syndrome.

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 Lynch syndrome. The study included 861 participants with Lynch syndrome—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 placebo.
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 placebo.
- 18 (4.2%) of individuals in the aspirin group developed colorectal cancer compared to 30 (7%) in the placebo group.
- 16 (3.7%) of individuals in the aspirin group developed other (non-colorectal) Lynch syndrome cancers compared to 24 (5.5%) in the placebo group.

At 4.5 years	Aspirin (n=427)	Placebo (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 placebo group.
However, no protection for other Lynch syndrome cancers was seen.
- 36 (8.3%) individuals in the placebo group and 36 (8.5%) in the aspirin group developed other (non-colorectal) Lynch syndrome cancers.
  - 17 women in the placebo 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)	Placebo (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 Lynch syndrome, 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) Lynch syndrome 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 placebo 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 Lynch syndrome.
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 Lynch syndrome. 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 Lynch syndrome.

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 Lynch syndrome, 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.

Share your thoughts on this XRAYS article by taking our brief survey.

posted 5/17/21

References

Burn J, Sheth H, Elliott F, Reed L, et al. Cancer prevention with aspirin in hereditary colorectal cancer (Lynch syndrome), 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 Lynch syndrome. 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 also relevant for:

people with a family history of cancer
people with a genetic mutation linked to cancer risk

IN-DEPTH REVIEW OF RESEARCH

Study background

Lynch syndrome is a syndrome that is caused by an inherited mutation in one of five genes: MLH1, MSH2, MSH6, PMS2 or EPCAM. People with Lynch syndrome 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 Lynch syndrome (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 Lynch syndrome to test a drug that may reduce cancer risk. Participants were randomly assigned to receive 600 mg/day of aspirin or a placebo 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 placebo, 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 Lynch syndrome. 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 Lynch syndrome. 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 placebo group. The aspirin group consisted of 427 participants who received 600 mg of aspirin daily for two years while the placebo 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 Lynch syndrome cancers. (The average follow-up time for all the participants at this time was almost 5 years.)
- 30 (7%) people in the placebo group developed colorectal cancer compared to 18 (4.2%) people in the aspirin group.
- 24 (5.5%) people in the placebo group developed other (non-colorectal) Lynch syndrome cancers compared to 16 (3.7%) people in the aspirin group. Of these:
  - 13 women in the placebo 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 placebo group developed colorectal cancer compared to 40 (9%) people in the aspirin group.
- While earlier results showed protection by aspirin for some non-colorectal Lynch syndrome cancers this finding was not statistically significant in the final analysis.
  - 36 (8.3%) people in the placebo group and 36 (8.5%) people in the aspirin group developed other (non-colorectal) Lynch syndrome cancers. Of these:
    - 17 women in the placebo group developed endometrial cancer compared to 7 women in the aspirin group but this was not statistically significant.

Lynch syndrome 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 placebo 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 Lynch syndrome.
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 Lynch syndrome. This requires a much larger study.
The specific Lynch syndrome gene mutations of the participants were not known. It is also unknown whether people with certain gene mutations had different outcomes than all Lynch syndrome 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 Lynch syndrome. 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 Lynch syndrome.

While aspirin has been linked to reduced risk of cancers, such as breast, prostate 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 randomized controlled trials are needed to confirm these findings.

Conclusions

The results of the CAPP2 study support the recommendation that adults with Lynch syndrome 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

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

Colorectal cancer

Colonoscopy every 1-2 years. Speak with your doctor about whether you should be screened yearly or every two years. Men, people over age 40 and individuals with a personal history of colon cancer or colon polyps may benefit most from yearly screenings.
- For people with MLH1, MSH2 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 MSH6 or PMS2:
  - beginning between ages 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 of colorectal cancer. The best dose and timing for aspirin are unknown. Speak with your doctor about the benefits, 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 between ages 30-35.
Discuss the benefits and risks of oral contraceptives.
Consider risk-reducing hysterectomy; discuss risk-reducing removal of ovaries and with your doctor (EPCAM, MLH1, MSH2 and MSH6 gene mutations).

Other cancers

Consider annual prostate cancer screening with testing and digital rectal exam.
For people with a family history of urothelial cancer and men with an MSH2 mutation:
- Consider annual urinalysis beginning between ages 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 category for gastric cancer.
Consider testing for H. pylori and treating if the test is positive.
For people with a family history of pancreatic cancer:
- Consider annual cholangiopancreatography (MRCP) and/or endoscopic (EUS) beginning at age 50.
- Consider participating in a pancreatic cancer screening study.

Consider annual physical and neurological exams.

Updated: 03/09/2023

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

The following screening and prevention studies are open to people with Lynch syndrome.

Colorectal cancer

NCT03831698: Omega 3 Fatty Acids in Colorectal Cancer (CRC) Prevention in Patients With Lynch Syndrome (COLYNE). This study assesses the effects of omega-3 acid ethyl esters capsules (generic Lovaza) on molecular and intestinal microbiota changes in participants at high risk for colorectal cancer.
NCT04379999: Atorvastatin ± Aspirin in Lynch Syndrome Syndrome. This study investigates whether a common cholesterol-lowering agent (atorvastatin) alone or combined with a nonsteroidal anti-inflammatory drug (aspirin) reduces the risk of colorectal cancer in high-risk individuals with Lynch syndrome.

Gynecologic cancers

NCT05257057: Frequency of Endometrial Cancer Precursors Associated With Lynch Syndrome. This study examines endometrial hyperplasia specimens and compares the frequency of Lynch syndrome gene mutations between people with endometrial hyperplasia and those with endometrial cancer.
NCT00508573: Registry for Women Who Are At Risk Or May Have Lynch Syndrome. This study facilitates the study of gynecologic cancer risks by creating a registry of information about women who have or are at risk for Lynch syndrome, to facilitate study of gynecologic cancer risks.
Validating a Blood Test for Early Ovarian Cancer Detection in High-risk Women and Families: MicroRNA Detection Study (MiDE). The goal of this effort is to develop a clinical diagnostic test to detect early-onset ovarian cancer, as currently, no reliable screening or early-detection tests are available.

Prostate cancer

NCT03805919: Men at High Genetic Risk for Prostate Cancer. This is a prostate cancer screening study using in high-risk men is open to men with Lynch syndrome and other mutations.
NCT05129605: Prostate Cancer Genetic Risk Evaluation and Screening Study (PROGRESS). This study looks at how well prostate MRI works as a screening tool for men at high risk for prostate cancer. Enrollment is open to men with an inherited mutation in , , , , , EPCAM, , MLH1, MSH2, MSH6, , , PMS2, , , and other genes.

Pancreatic cancer

NCT02206360: Pancreatic Cancer Early Detection Program. This pancreatic cancer screening study uses esophageal ultrasound to screen for pancreatic cancer in high-risk people. The study is open to people who have a family history of pancreatic cancer and an MLH1 mutation or other mutation linked to increased cancer risk.
NCT03568630: Blood Markers of Early Pancreas Cancer. This pancreatic cancer study involves blood samples taken over time to identify biomarkers of pancreatic cancer in high-risk people. Enrollment is open to people with an MLH1 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. MRI and magnetic cholangiopancreatography (MRI/MRCP) will be utilized to screen for pancreatic lesions.

Other clinical trials for patients with endometrial cancer can be found here.

Updated: 03/09/2023