Inflammatory Bowel Disease and Colorectal Cancer

By Lois Zoppi, B.A.

People with inflammatory bowel disease (IBD) have a higher risk of developing colorectal cancer (CRC), commonly termed bowel cancer.

The reasons for IBD-associated colorectal cancer are not known. For the past decade, the incidence of CRC has been decreasing in the Western World, but in Asian countries, it has been on the rise. The incidence of IBD in these countries is also on the rise, suggesting the two may be linked.

CRC accounts for 1% to 2% of all cancers and is a serious complication of IBD that accounts for around 15% of IBD deaths. The risk of CRC remains in periods of IBD remission.

What is colorectal cancer?

Colorectal cancer is cancer which originates in the colon or the rectum. Symptoms include:

• Changes in one’s normal bowel movements
• Blood in stool
• Bleeding from the rectum

It can begin in the large intestine (colon) or the rectum. There are a number of treatment options for colorectal cancer, including surgery, radiotherapy, or chemotherapy. A combination of these treatments can also be used. The following risk factors are associated with colorectal cancer:

• Age
• Family history
• Lifestyle
• Other medical conditions

You can find a more in-depth article on colorectal cancer here.

What is inflammatory bowel disease?

Inflammatory bowel disease is an umbrella term for a number of disorders that involve inflammation of the digestive tract, namely ulcerative colitis (UC) and Crohn’s disease (CD).

IBD is characterized by the following symptoms:

• Diarrhea
• Fever
• Fatigue
• Abdominal pain
• Blood in stool
• Reduced appetite
• Unintended weight loss

The range and severity of symptoms may vary depending on where the inflammation occurs. People living with IBD often experience periods of remission in between periods of active illness.

Poor diet and stress were previously thought to be among the immediate causes of IBD. However, it is now believed that while diet and stress may aggravate or worsen IBD, they are not causative factors.

Risk factors for IBD include:

• Age
• Race and ethnicity
• Family history
• Smoking
• Living location
• Nonsteroidal anti-inflammatory medications

Causes of CRC in IBD

Although it doesn’t provide a full explanation, there is increasing interest in the potential for IBD-associated CRC to be caused by genetic alterations. Genetic causes of CRC are different for sporadic versus IBD-associated CRC.

Changes in DNA methylation and microsatellite instability are often detected in the early stages of CRC-associated with ulcerative colitis, and loss of heterozygosity (loss of heterozygosity; where one of the two gene copies in a cell is altered) is common.

An association between a common gene variant (the G308A TNF-α polymorphism) and UC-associated CRC has also recently been made, which reinforces the connection between chronic inflammation and CRC pathogenesis.

There is also evidence to suggest that certain cytokines released by epithelial and immune cells are involved in the pathogenesis of IBD-associated neoplasia.

Tumour growth is promoted by TNF-α and IL-6-induced signalling, and two protein complexes, cyclooxygenase-2 (COX-2) and nuclear factor kappaB (NF-кB), are both involved in the inflammatory process and provide a connection between inflammation and cancer.

Risk factors

The following factors increase the risk of developing IBD-associated CRC:

• Duration of IBD
• Extent of colitis
• Coexistent primary sclerosing cholangitis (a rare complication involving inflammation of the ducts that drain the liver)
• Young age at diagnosis

Family history and the severity of inflammation are also recognised risk factors.

Family history of CRC

Those with a family history of sporadic CRC double the risk of developing CRC compared with patients with no family history of CRC. Studies have shown that people with a first-degree relative with CRC before the age of 50 also had a higher risk of CRC.

Severity of inflammation

Inflammation is believed to promote carcinogenesis, but studies investigating the correlation between increased severity of chronic inflammation and CRC are lacking.

While the pathogenesis of IBD-associated CRC is not fully understood, there are similarities with sporadic colorectal cancer, for instance, CRC in both instances are due to sequential episodes of genomic alteration.

Other factors involved in the pathogenesis of IBD-associated CRC are immune responses to mucosal inflammatory mediators, oxidative stress and intestinal microbiota.

Decreasing the risk of CRC

There are a number of methods for decreasing the risk of CRC, including:

• Scheduling regular check-ups with a gastroenterologist
• Exercise
• Maintaining a healthy diet
• Remaining on medications regardless of remission periods
• Taking medications to control the inflammation of IBD

Diagnosis

As with many cancers, early diagnosis is key in decreasing the risk of CRC. Options for this include colonoscopic surveillance and treating precancerous lesions. However, evidence for the effectiveness of preventative surveillance methods are yet to be definitively proved.

Treatment

Ongoing inflammation of the colon is thought to be associated with the development of CRC. Anti-inflammatory agents such as 5-aminosalicylate compounds (5-ASAs) and immune modulators have been considered for preventative treatments.

Ursodeoxycholic acid (UDCA), folic acid and certain immunosuppressive drugs have been identified as potential chemopreventives in IBD.

Scanning for colorectal cancer with colonoscopies is also an accepted preventative method, but there is no evidence that it extends life expectancy.

Further Reading

• All Inflammatory Bowel Disease Content
• What is Ulcerative Colitis?
• Ulcerative Colitis Causes
• Genetics of Inflammatory Bowel Disease (IBD)
• Inflammatory Bowel Disease (IBD) in Pregnancy