Overview

Inflammatory Bowel Disease (IBD) is an autoimmune disease that involves abnormal immune responses to the intestinal microflora. The underlying cause of IBD remains elusive even until now.¹ Nevertheless, the continuous interplay between IBD and colorectal cancer (CRC) has been documented over the years, with statistics demonstrating a strong correlation between the two. In this article, we will investigate the intricacies between IBD and CRC, encompassing the manifestations, risk factors and preventive measures for IBD-associated CRC. 

Overview of inflammatory bowel disease (IBD)

IBDi is a chronic relapsing inflammation of the gastrointestinal tract. It is categorised into two different forms namely, Ulcerative Colitis and Crohn’s Disease. The two diseases are defined based on the site of inflammation along the gut wall.¹ Ulcerative Colitis describes a colonic mucosa inflammation that primarily occurs at the rectum and could potentially extend upstream to the caecum.^1,2 Crohn’s Disease on the other hand, usually affects the small intestines and first segment of the colon, but the inflammation may also take place at any part of the gastrointestinal tract, involving all layers of the intestinal wall. Due to this nature, its initial manifestations can be relatively less pronounced than those of Ulcerative Colitis.³  

In 2020, the prevalence of IBD in the UK was approximately 0.8%, which is equivalent to about 1 in every 123 people diagnosed with IBD. This can be further broken down into the different entities of IBD, with Ulcerative Colitis being the most common form of IBD (0.4%), followed by Crohn’s Disease (0.3%), and lastly, unclassified IBD (Indeterminate Colitis)  with the least prevalence of 0.07%. IBD is more widespread in developed countries, northern climates, and urban regions. Historically, IBD is regarded as a disorder that generally affects patients of Western or European ancestry. However, due to demographic changes and socioeconomic developments over the decades, the prevalence of IBD has rapidly changed worldwide, leading to increasing incidence rates of IBD observed in Asia, South America and Africa as well.⁷ The aetiology of the two entities of IBD remains obscure; however, many studies have depicted significant influence by several factors, including genetic predisposition, environmental factors and gender. A study concluded that Crohn’s Disease demonstrated higher incidence rates among females, while Ulcerative Colitis patients showed no significant difference between genders.⁸

Both of the diseases share some similar symptoms including:¹ 

• Diarrhoea (sometimes with blood or pus)
• Weight loss
• Fatigue
• Abdominal pain
• Fever

You might think, if both diseases share the same symptoms, how are we supposed to determine if the IBD is more likely Ulcerative Colitis or Crohn’s disease? Apart from the symptoms they share, they still possess some distinct presentations that help us distinguish between the two. For instance, bloody diarrhoea (sometimes with pus) is mainly associated with Ulcerative Colitis, as well as pain in the lower left part of the abdomen. Conversely, the common manifestations of Crohn’s Disease include pain in the right lower quadrant of the abdomen and non-bloody diarrhoea. The symptoms of Crohn’s disease will also vary accordingly depending on the location of ulceration along the gut tract.¹  

Moreover, extraintestinal manifestations are prevalent in approximately 25-40% of all IBD patients. The common primary manifestations include inflammation of the skin, eyes and joints.⁴ Those associated with Ulcerative Colitis include episcleritis, peripheral arthropathies, ankylosing spondylitis etc., whereas extraintestinal manifestations in Crohn’s disease include arthritis, uveitis and renal dysfunctions that may precede intestinal infections.^2,3 

While these two diseases are usually distinguishable, approximately 5-15% of IBD patients do not specifically fit into either criteria of Ulcerative Colitis or Crohn’s disease. These patients will then be classified as Indeterminate Colitis.⁵ 

Diagnosis of IBD usually starts off with the examination of the aforementioned clinical symptoms. However, to accurately determine Ulcerative Colitis or Crohn’s Disease, gastrointestinal endoscopy, stool testing, complete blood count and colonoscopy are utilised. Radiography is also effective in detecting the precise location of the gastrointestinal tract that is affected by Crohn’s Disease. With these physical tests and laboratory analyses being employed, the form of IBD can be diagnosed precisely, not to mention rare and severe infections that are hardly distinguishable. Also, regular endoscopies are required for patients with IBD due to its high-risk nature of developing colon cancer.⁶ 

The relationship between IBD and colorectal cancer

Colorectal cancer (CRC) is ranked as one of the most common cancers worldwide, contributing to about 10% of all cancer cases. Patients diagnosed with CRC can experience severe outcomes, and it is also the second-highest death-causing cancer worldwide. The risk of developing CRC increases with age, however, there is another group of people that are also at high risk of developing this cancer --- IBD patients. 

IBD patients, regardless of Ulcerative Colitis or Crohn’s Disease, are exposed to a high risk of developing colorectal cancer (CRC) due to chronic persistent inflammation in the intestinal tract resulting in DNA oxidative stress injury.⁹ CRC has contributed significantly to the mortality rate of IBD, accounting for approximately 15% of mortality in IBD patients. Interestingly, recent studies have elucidated the declining prevalence of CRC in IBD over the past three decades.¹⁰ Despite that, it is undeniable that IBD patients stand a higher chance of developing CRC as compared to the general population. CRC frequency rates among IBD patients and the general population are analysed with the latter (1.23%) being lower than the former (1.78%).¹¹ 

As IBD is an autoimmune disease, treatments administered act to induce mucosal healing by inhibiting the ‘self-destructing’ immune response. However, immunosuppressive treatments often lead to the occurrence of neoplastic adverse events, leading to uncontrolled proliferation of intestinal epithelial cells, ultimately resulting in tumour growth.¹² Unlike the usual progression sequence of sporadic CRCs, the development of IBD-CRC follows a different pattern specifically, the ‘inflammation-dysplasia-carcinoma’ sequence. The relapsing nature of IBD inflammation escalates the evolution and instigates genetic mutations, subsequently resulting in the malignant progression of the intestinal epithelium, thus, driving mutagenesis. This explains the high frequency rate of CRC among IBD patients.¹³ 

Risk factors for colorectal cancer in IBD patients

Despite having a higher frequency rate of CRC compared to the general population, most IBD patients have a slim chance of contracting CRC. However, it is paramount to be aware of the risk factors that contribute further to the increase in the occurrence of CRC in IBD patients. The risk factors identified are as follows:⁹ 

• Patients diagnosed with IBD at an earlier age (<30 years old) 
• Length of duration being diagnosed with IBD 
• Length of colon infected in IBD patients (Pancolitis)
• IBD patients with a family history of CRC 
• IBD patients who are also diagnosed with Primary Sclerosing Cholangitis (PSC)       

Preventive therapeutics and early detection

The increased risk of CRC among IBD patients has always been highlighted in various studies over the years. Despite this, for the past three decades, several studies have observed a decline in the incidence rate of IBD-CRC. This is largely attributed to early screening procedures and advanced treatment interventions for preventing CRC.¹⁰

IBD patients who fall in any of the high-risk factor categories will have a more frequent surveillance schedule with more frequent colonoscopies and often at a younger age for early detection of dysplasia. The British Society of Gastroenterology (BSG) endorsed pancolonic chromoendoscopy for all IBD-CRC surveillance protocols, and the recommended frequency of colonoscopy ranges from every 1, 3 and 5 years depending on the level of risk according to their risk groups.⁹ 

Some anti-inflammatory treatments are employed to control the inflammation, thus indirectly reducing the chance of developing CRC in IBD over time. These therapeutics often possess chemopreventive effects that can effectively control mucosal inflammation, thus minimising the risk of CRC.¹⁰

• Aminosalicylates (5-ASA) (mesalamine, sulfasalazine, olsalazine)
• Thiopurines
• Biologics (Vedolizumab)

Summary

Given the high risk of contracting CRC, early screenings and preventive treatments have to be implemented in hopes of improving the prognosis and significantly reducing the risk of developing IBD-CRC. Although the incidence rate of IBD-CRC is gradually decreasing over the years, IBD patients are still more susceptible to developing CRC than the general population. Hence, the public, especially IBD patients are encouraged to engage in preventive measures and to constantly consult their GP regularly about their risks of developing CRC. Furthermore, through continuous efforts in this field of study, more novel therapeutic targets, advancements in diagnostic techniques and therapeutic interventions can be invented to enhance the management and quality of life of IBD patients, ultimately alleviating the influence of IBD-CRC on public health.¹⁴