Introduction 

Inflammatory bowel disease (IBD) is an umbrella term for diseases that cause chronic (long-term) inflammation of the digestive tract, in particular- Crohn’s disease and Ulcerative Colitis. 

Having IBD does increase the risk of certain types of cancers including: colorectal cancer, but also small bowel cancer, intestinal lymphoma, and cholangiocarcinoma. 

What is inflammatory bowel disease?

Inflammatory bowel disease refers to diseases that involve inflammation of the bowel- namely Crohn’s disease and ulcerative colitis.^7,8 As shown in the picture (source), the term ‘large bowel’ refers to the large intestine, and the term ‘small bowel’ refers to the small intestine. IBD most commonly affects the large intestine. 

There is no known cause, but IBD can run in families (although there isn’t any single gene that causes it) and smoking can add to the risk. IBD is most commonly seen in urban, European and North American populations, although the cases are rising in Asian populations too.⁸

Symptoms include blood and/or mucous in stools, severe abdominal pain, diarrhoea, and weight loss (unintentional). IBD is a relapsing and remitting disease. This means that the disease will have phases of flare ups (relapse). With treatment, the disease can subside, this is known as remission where there are no signs or symptoms of the disease.

Usually, IBD is diagnosed in 15 to 25-year-olds, but there is no set timeline as to when the flare-ups will happen, and some flare-ups are more severe than others- but again there is no rule as to how severe each flare-up will be.⁸

IBD, due to its severe and unpredictable nature, can have a serious effect on the person’s quality of life. 

It is worth noting that IBD is not the same as IBS (irritable bowel syndrome). IBS involves some changes in bowel habits such as diarrhoea, constipation, bloating, etc, however, there is no inflammation of the bowel. 

Ulcerative colitis is the most commonly occurring inflammatory bowel disease.⁷ It involves inflammation and ulceration of the colon (large intestine and rectum). It may not involve the entire large intestine at the same time, there may just be some parts of it that are affected. 

Crohn’s disease, unlike ulcerative colitis, can affect any part of the digestive tract from the mouth to the perianal (around the anus) area, however, it most commonly affects the large intestine and the end of the small intestine.⁷

The below images are taken from colonoscopies (where a camera is inserted into the colon). The image on the left (source) shows a normal colon where the lining is pink and smooth. The image on the right (source) shows a case of ulcerative colitis where the lining is raised, irritated, and the ulcerated lesions can be seen.

Chronic inflammation can damage the bowel and cause proinflammatory molecules such as cytokines, reactive oxygen species (ROS), tumour necrosis factor-alpha (TNF-a), and some interleukins that can be present over long periods of time with IBD. Repeated, long term damage and repair of the areas can result in something going wrong during cell division and repair and the previously mentioned inflammatory molecules can also facilitate the formation of cancer cells.

Colorectal cancer 

Colorectal cancer is the most commonly occurring cancer due to IBD, and usually, this is with ulcerative colitis. Colorectal cancer is the third most commonly occurring type of cancer globally and the cause of this is chronic inflammation which damages the tissue.^1,2,3 There is one gene called p53 whose function it is to stop uncontrolled cell division and is involved in the process of killing cells that may have been made with faulty DNA. In about half of all human malignancies, including around 85% of colitis-associated cancers, the p53 gene is mutated.⁴ 

The main risk factor for cancer is the duration of the disease in the person. In one large study, colorectal cancer risk in ulcerative colitis has been reported to be 2% after 10 years, 8% after 20 years, and 18% after 30 years of disease. Diet is also associated with colorectal cancer risk- red meats, trans fats, and fast foods were most strongly associated with p53 mutations. There was also evidence to suggest that vegetarian diets lower the risk of colon cancer.⁵

Symptoms of colorectal cancer include blood in stools, unintentional weight loss and a change in bowel habits (for anyone over the age of 60, with a new-onset change of bowel habits, testing should be done for colorectal cancer, although this is not the only age group that this cancer can occur in).^6,7

Because of the increased risk of colorectal cancer with IBD, those who have IBD generally have surveillance colonoscopies- these are screening appointments to check the colon to see if there are abnormalities.² Guidelines on frequency vary from country to country but generally start 8-10 years after initial diagnosis, and then occur every 1-3 years.

‘Dysplasia’ is the term used to describe an area that contains cells that have changed from their normal appearance. Sometimes dysplastic cells can turn into cancer cells, but this does not always happen- they may go away on their own, or remain in the same form. Dysplasia can often be difficult to detect in IBD cases if the colon is inflamed or ulcerated to begin with.⁶ 

If there is an area of dysplasia seen, there will usually be a biopsy of the area taken- this is a small sample of cells to be examined under a microscope to detect whether or not there are any cancer cells present. If there is no sign of cancer, then the area will be monitored at more frequent screening appointments. If cancer is found, its management will be dependent on the stage that it is found- i.e how big the tumour is and whether or not there is any spread. Surgical removal of the affected area can be an option in some cases. Chemotherapy and radiotherapy are also common treatment modalities. 

Other cancers 

There are three other types of cancers which have an increased incidence with IBD, which are less commonly occurring than colorectal cancer.³ 

Small bowel carcinoma 

Small bowel carcinoma is cancer of the small intestine. It is around 20 to 30 times more common in people with Crohn’s Disease as compared to the general population. Treatment is usually a combination of surgical removal of the affected area along with chemotherapy and radiotherapy.¹⁰ 

Cholangiocarcinoma

Cholangiocarcinoma is a cancer of the bile duct- the tube that takes bile from the liver into the small intestine. It is a very rarely occurring cancer, but there is a known relationship with IBD and cholangiocarcinoma. Symptoms include jaundice, severe abdominal pain, and weight loss- symptoms that can overlap with an IBD flare-up. Generally, the prognosis of this cancer is not good, especially for those with underlying IBD.¹⁰

Intestinal lymphoma 

Intestinal lymphoma refers to cancer of the lymph nodes which are in the intestinal area, usually a form of Non-Hodgkin’s Lymphoma (the other form of lymphoma is known as Hodgkin’s Lymphoma). This is a very rare complication of IBD and the risk can be increased with certain medication combinations. Symptoms include enlarged lymph nodes, fever, night sweats, and weight loss. Still, the risk of actually getting lymphoma is very small. Prognosis is very much dependent on the stage it is found- with earlier stages having a much better outcome.¹⁰ 

Treatment of IBD

Treatment of IBD can involve medication. Common types are:^2,7,8,9

• Aminosalicylates- used to control inflammation of the bowel
• Corticosteroids- used in flare-ups of IBD to control inflammation; not usually used as maintenance therapy 
• Immunomodulators- a common one is methotrexate, used for maintenance of remission also includes thiopurines 
• Biologic agents- common drugs are infliximab, adalimumab, vedolizumab, and ustekinumab; infliximab and adalimumab target the TNF-a protein and help to reduce inflammation 

With treatment, function can sometimes be restored and the disease can enter remission, where there are no symptoms. However, some severe cases do not always respond to treatment. In these situations, surgical removal of the colon (or part of the small intestine) may be an option. 

Role of medication in cancer 

Thiopurines carry a very small increase in the risk of lymphoma, although because this risk is small, it is usually offset by the benefits of maintaining remission. This risk has been seen to be amplified when taking thiopurines in addition to a biological agent; however, it is still very small and there is not enough data to draw definitive conclusions. Overall, the absolute risk of cancer as a consequence of medication is very small compared to the risk of cancer from IBD.³

Summary 

Crohn’s disease and ulcerative colitis are collectively known as Inflammatory Bowel Disease. Having IBD does increase the risk of cancer- particularly colorectal cancer. The longer someone has IBD, the greater their risk of colorectal cancer. Regular surveillance colonoscopies are carried out to examine the colon and aim to identify any abnormalities as early as possible. Modifiable risk factors for cancer are smoking and diet - not smoking and avoiding red meats, processed food, and trans fats will reduce the risk of colorectal cancer.