Introduction

Imagine hearing that you have a genetic syndrome that increases the likelihood of developing cancer. How would you feel? What would your first thought be? After initially feeling overwhelmed and asking yourself ‘What is next?’, you might then wonder, ‘What could I do to prevent this?’. Regarding Muir-Torre Syndrome (MTS), several straightforward lifestyle interventions are shown to prevent MTS-related cancers.

What is Muir-Torre syndrome?

Muir-Torre Syndrome, a subtype of Lynch Syndrome, is a genetic disorder that is known to increase risk for the development of several types of cancer. While it is rare, and there are only about 200 recorded cases, the true prevalence may not be known since the documented cases were in a mostly white population in first-world countries.¹ 

If a parent has MTS, there is a 50% chance that their child will also have it. Several different gene mutations may cause MTS due to an inability to repair DNA correctly once it has been damaged. Another condition, called hereditary non-polyposis colorectal cancer, can also result from the same gene mutations.¹

MTS is linked to the development of several different types of non-cancerous skin tumours, including sebaceous adenomas, Fordyce spots, and keratoacanthoma. While most of the skin growths are not cancerous, sebaceous carcinomas can be.¹ 

The bigger concern is the development of internal cancerous lesions. This is most likely to occur in the gastrointestinal tract (specifically, the colon and rectum) and is usually present about 15-20 years earlier than non-MTS-related colon cancers. Diagnosis usually occurs at around 50 years old, and these tumours may grow more quickly than colon cancers in people without MTS.¹ 

MTS is a special type of Lynch Syndrome, known to cause an increased risk of several cancers, including colon cancer. The following cancers are more common in someone with MTS:¹

• Stomach cancer
• Urinary tract cancer
  • Kidney 
  • Bladder 
  • Ureters (tubes connecting the kidney and bladder)
  • Urethra (tube through which urine exits the bladder)
• Uterus

Many other cancers could be caused by MTS, but the frequency is not quite as high as previously mentioned. However, almost 60% of patients with an MTS-related cancer will develop metastatic, or widespread, cancer and about half will develop more than one cancer.

Importance of prevention strategies for MTS-related cancers

Since MTS is inherited in most cases, cancer prevention is critical. Some strategies can be used, and have been backed up with previous evidence. These include appropriate colorectal cancer screening, dietary changes, and the use of aspirin. Based on the statistics regarding the development of more than one cancer, and the increased risk that any cancer will become metastatic, prevention is the best option.^2,3

Types of cancers associated with MTS

Skin growths, some non-cancerous and some cancerous, are the most usual symptom of MTS. Colorectal, urinary, uterine, and stomach cancers are the most likely internal cancers. However, there are many other cancers, which may be more likely to occur as well. These include, but are not limited to:¹

• Breast
• Prostate
• Liver
• Ovarian
• Brain
• Lung

Incidence rates

About 30-79% of MTS patients will develop stomach or colon cancer. Likewise, 5-29% will develop breast or uterine cancer. Finally, 80-99% will develop the non-cancerous sebaceous adenoma.

Prevention strategies

Genetic counselling and testing 

Importance

In this case, before trying to conceive, an individual with MTS, or with a family history of MTS, should opt for genetic counselling to discuss reproductive planning. Since there is a 50% chance that a parent with MTS will pass it to any offspring, this is an important decision. In this case, individuals with MTS could be referred to other specialists if they would like to have biological children or encouraged to investigate other pathways to become a parent.⁴

Benefits of genetic testing for early detection and intervention

Genetic testing to determine if a person has a gene mutation leading to MTS can prompt additional screening for MTS-related cancers and begin a process regarding prevention and risk reduction. DNA sequencing is the standard genetic testing. Preventative screening schedules will be more rigorous, and implemented earlier than it would be for similarly aged individuals without a history (personal or family) of MTS.⁴ 

Screening tests 

Due to the potential for numerous cancer types of various body locations, there are many potential screening tests available. However, since the most common types of MTS-related cancers are concerning the skin, colon, uterus, urinary tract, stomach, and the breast, many of the screening exams focus on those specific areas.^4,5

Recommendations

• Colonoscopy – starting at age 25-30; every 3-5 years
• Upper gastrointestinal (GI) endoscopy (if there is a history of upper GI cancers) starting at age 30-35; every 3-5 years
• Mammogram – starting at age 50; every 1-2 years
• Pap smear – starting at age 25; every 3-5 years
• Endometrial (uterine) biopsy – starting at age 50; every 3-5 years
• Urinalysis – yearly
• Blood tumour markers – yearly (depending on the patient-specific risk)
• Dermatology exam – yearly^4,5

These guidelines can help prevent MTS-related cancers and detect them in the earlier stages should they develop.^4,5

Lifestyle

Two specific lifestyle changes might help prevent cancers if suffering from MTS: eating a diet high in resistant starch, and taking aspirin daily. There is also newer data showing that exercise can help reduce risk of developing cancers in Lynch syndrome, so there is a good chance that this could apply to MTS also.^2,3

Resistant starch diet 

A diet high in resistant starch is thought to lower the risk of developing gastrointestinal cancer because of the high amounts of fibre. Higher fibre foods are not digested in the small intestine, and undergo fermentation in the bowel, producing a byproduct (butyrate) which has been shown to have a preventative effect against cancer. Interestingly, the risk of colorectal cancer did not change when adding resistant starch, but the risk of other MTS-related cancers did decrease. This was noted especially in the upper gastrointestinal tract, including the stomach, small intestine, and the bile duct.²

Resistant starch foods include:²

• Slightly under-ripe bananas
• Potatoes
• Beans, lentils, chickpeas, and dried peas
• Wheat, oats, and other grains
• Seeds

Preventative aspirin 

Aspirin has been shown to be effective at reducing the risk of developing MTS-related cancers in several clinical trials. However, since the main side effect of aspirin is an increased risk for bleeding, the individual with MTS needs to have a thorough conversation with their doctor about risks and benefits before starting a daily aspirin regimen.^2,3

The research studies have shown that there is between a 40-49% decrease in the risk of death starting at five years after taking aspirin for colorectal cancer prevention. Even a dose of 75 milligrams per day, which is recommended for those with an increased risk of heart disease, showed a benefit to preventing cancer. It is believed that the anti-inflammatory mechanism of aspirin may be the root cause for the risk reduction seen in gastrointestinal cancers.^2,3

Exercise

Recent research has shown that exercise can be connected to colorectal cancer risk reduction in Lynch syndrome. Sustained aerobic cycling exercise may activate the immune system and increase the recognition and removal of cancerous growths in the colon. Genetic testing showed changes in numerous genes in the tissue lining the colon, which are known to activate the immune system. While this needs more investigation to better understand this effect of exercise on cancer prevention, it might present a straightforward non-pharmaceutical option for people suffering from Lynch syndrome, and this could also be relevant for the prevention of MTS-related cancers.⁶

Prophylactic surgery 

In the case of the more common MTS-related cancers, some risks can be reduced by removing the area where potential tumours may develop. Prophylactic surgery would be helpful in preventing breast, colon, ovarian, or other types of cancer. Of course, this does not eliminate all risks since MTS-related cancers can also occur on the skin, and in almost every other organ. While there may be benefit in an individual with MTS, there is also risk associated with surgery, and the decision to remove an organ to prevent cancer should only be made after careful consideration of the patient and their case physician.²

Summary

Muir-Torre syndrome is an inherited condition which increases the risk of developing cancer. While the most prevalent cancer types are colon, stomach, urinary, and uterine cancer, nearly every organ is at risk. There are several promising methods to prevent, and reduce the risk of developing MTS-related cancers. These include:

• Genetic counselling, which educates the MTS patient about the risk of developing cancer, and about the risk of passing on MTS to their offspring
• Preventative surgery to remove an organ that has a high probability of developing cancer
• Diet with high fibre and resistant starches
• Daily use of aspirin
• Regular, higher intensity exercise

All of the above methods can be used to reduce risk and prevent MTS-related cancers.