Introduction

Gastrointestinal (GI) cancers are a group of cancers that affect the digestive system, including the stomach, oral, small intestine, large intestine, esophageal, liver, pancreas, and colorectal cancers. These cancers represent a large portion of cancer diagnoses, accounting for around one quarter of diagnoses and almost one third of cancer-related deaths.¹ One rare genetic condition that significantly increases the risk of developing GI cancers is Muir-Torre syndrome (MTS).² 

MTS was first described by Muir et al in 1967 and, independently, by Torre et al one year later, in 1968. MTS is a rare hereditary disorder considered a subtype of Lynch syndrome. That is inherited in an autosomal dominant pattern, meaning that a child has a 50% chance of getting the disease if the parent has the mutated gene. MTS causes tumours to form in the oil glands in the skin and at least in one internal organ. Skin tumours usually occur on the face, scalp, and eyelids. These skin tumors can develop as cancerous or noncancerous (benign). Furthermore, the internal organ tumours usually develop in the gastrointestinal tract (especially the colon and rectum). 

MTS is a genetic disease caused by mutations (changes within the DNA sequence), the mutations involve changes within the MLH1, MSH2, or MSH6 gene. These genes are mismatch repair genes, meaning they are involved in correcting mistakes made when DNA is copied in a cell, cells deficiency in mismatch repair usually acquire many mutations, which may lead to cancer. Often these mismatch repair genes acquire missense mutations (a single nucleotide base in DNA sequence is swapped for another, resulting in a different codon meaning a different amino acid), which most commonly involves the MSH2 gene. The mismatch repair genes listed above are known as ‘tumour suppressor genes’, which act as the brakes to cancers and stop the growth of tumours. The genes prevent cancers through providing instructions for synthesizing a protein that plays a role in repairing DNA. Therefore, when these tumour suppressor genes undergo loss of function mutations, as in MTS, tumour cells accumulate. 

MTS is a very rare disease, only around 200 cases have been recorded, occurring mostly from white population in developed western nations.³ Also, MTS appears to be slightly more prevalent in people assigned male at birth (AMAB) than in people assigned female at birth (AFAB). Due to the rarity of the condition, there is less clinical data and fewer research studies available on MTS, but this article will aim to provide all the essential knowledge on the topic.

Gastrointestinal cancers linked to MTS

GI cancers include a wide variety of malignancies that affect different parts of the digestive system. GI cancers are common and deadly cancers within the general population, making early detection and prevention crucial. However, for individuals with MTS, the risk of developing GI cancer is significantly higher.

Colorectal cancer

The most prevalent GI cancer associated with MTS is colorectal cancer – a cancer that starts in the colon or rectum, accounting for around half of the cases. Patients with MTS have a 60-80% lifetime risk of colorectal cancer, they also commonly develop the cancer 15 to 20 years earlier than it usually does, with the average age of onset being 50 years old.⁴ Regular screening methods like colonoscopies are recommended for early detection and prevention, especially if you are at high risk.

Small intestine cancer

Secondly, another GI cancer commonly linked to MTS is small intestine cancer, accounting for about 4% of cases.⁵ Within the general population, this is a relatively rare cancer. Within 2017-2019, there were around 1,900 small intestine cancer cases within the UK every year. Sadly, due to the rarity, small intestine cancer is often diagnosed at a later stage, highling the importance of regular screening in MTS patients.

Gastric cancer

Gastric (stomach) cancer is also associated with MTS. Gastric cancer approximately occurs in 1 person in every 10,000 people, defining this as a ‘rare disease’. However, this type of cancer has a higher incidence in MTS patients. 

Genitourinary cancer

MRS also can result in other internal malignancies such as genitourinary cancers – involving the urinary tract and male reproductive organs (urinary bladder, penis, prostate, renal and urinary tract).

Symptoms and diagnosis of GI cancers and MTS

The symptoms of MTS often include skin lesions, which often serve as early warning signs. These lesions include sebaceous adenomas, sebaceous carcinomas, and keratoacanthomas. The presence of these skin tumors, alongside a family history of Lynch syndrome-related cancers, can prompt further genetic evaluation for MTS. Immunohistochemistry is now being used to diagnose patients with MTS by identifying defects in the mismatch repair genes i.e MLH1, MSH2, MSH6 genes. 

The symptoms of GI cancers can vary depending on the specific type. However, the general symptoms associated with GI cancers are present. This includes abdominal pain, changes in bowel habits (such as constipation or diarrhoea), unexplained weight loss, and fatigue. Furthermore, small intestine cancer can include symptoms like jaundice (yellowing of your eyes or skin), bloating, and dark bloody stools indicating gastrointestinal bleeding.

Diagnosis of GI cancers in MTS patients typically involves a combination of tests, based on symptoms and health tests: imaging tests (CT, MRI, or PET scans), blood tests (such as carcinoembryonic antigen), and colonoscopy (often used for detecting colorectal cancer).

Treatment and management

The treatment for patients with GI cancers often depends on their type and evolution stage. Although, common treatments include:

• Surgery: This is highly effective for treating localised cancers. These procedures are very complex, requiring highly skilled GI cancer surgeons. Surgery can also be combined with other GI cancer treatments, like chemotherapy. Additionally, surgical removal of the tumour is used as first-line treatment
• Radiotherapy: Uses high-energy X-rays to kill cancer cells
• Chemotherapy: Uses specific drugs to target cancer cells; but this type of treatment contains many side effects as it targets normal/healthy cells, especially cells with high rates of division (such as hair follicles). This is why patients receiving chemotherapy usually lose their hair
• Immunotherapy: A new area of treatment showing very promising results in many types of cancers. This type of treatment works by reactivating the immune system to fight the cancer cells. For example, nivolumab can be used in people with advanced stomach cancer and it’s shown to improve overall surviva⁶

Often for MTS, oral isotretinoin (sold under the brand name of accutane) can be given to patients to prevent some of the formage of neoplasms.⁷

For MTS patients, treatment plans need to be tailored to their genetic profile and cancer risk. Regular screening methods and surveillance is essential for early detection of GI cancer. Early detection of cancer when it isn’t too large and hasn’t spread to other parts of the body makes treatment more effective. This is why the NHS provides regular cancer screenings for people with MTS.

Living with MTS and GI cancer

Living a life with MTS and GI can be challenging, both physically and emotionally. Patients often require multidisciplinary care teams such as oncologists, dermatologists, geneticists, and gastroenterologists to provide comprehensive care. Support resources, such as patient support groups and counselling services, can help patients and their families cope with the diagnosis and treatment process.

FAQs

What is Muir-Torre syndrome (MTS)? 

MTS is a rare hereditary condition characterised by the presence of sebaceous gland tumours and internal malignancies. It’s a subtype of Lynch syndrome and is caused by mutations in DNA mismatch repair genes.

What genes are involved in MTS? 

MTS is primarily associated with mutations in MLH2, MSH2, and MSH6 genes. However, 90% of the cases occur due to a mutation in MSH2.

Can MTS be cured?

MTS cannot be cured due the condition's genetic nature. However, regular screening and early detection can help prevent the associated conditions of MTS. 

Summary

Understanding the increased risk that having MTS poses on GI is vital for patients to understand. This is to make sure they are extra careful checking for malignancies, thus being able to effectively spot the cancer in the earlier stages which will ultimately lead to effective treatment. By recognising the signs and symptoms, utilizing genetic testing, and employing various treatment methods, healthcare providers can significantly improve the quality of life and survival rates for patients with MTS.