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Inflammatory bowel disease (IBD) is a group of inflammatory conditions that affect the gastrointestinal (GI) tract.* The main types of IBD are Crohn’s disease and ulcerative colitis. IBD affects less than 1% of the western world and typically begins to manifest in adolescence. Although ulcerative colitis is restricted to the bowels, Crohn’s disease can manifest anywhere along the GI tract.

IBD is considered to be an autoimmune disease. This means the body’s immune system incorrectly targets cells that are native to the GI tract. As a result, cells and tissues can be damaged or destroyed. This in turn can cause organs to malfunction.  Due to the dysregulation of the immune system, and the associated inflammation, patients with IBD are at an increased risk of developing intestinal and extra-intestinal (other than the intestines) cancers.

3D medical animation still showing Irritable bowel syndrome and tenesmus in the pip.
3D medical animation still showing Irritable bowel syndrome and tenesmus in the pip. (CC BY-SA, http://www.scientificanimations.com/ Wikimedia Commons)

In terms of treatment, the primary therapeutic agents target the immune system. Examples of commonly used medications for IBD include:

  • Immunomodulators (primarily immunosuppressors – drugs that diminish the functioning of the immune system) 
  • Anti-tumour necrosis factor agents
  • Anti-integrin therapy

Some of the drugs used to treat IBD can alter cellular DNA, thereby causing cancer.

IBD and cancer

Over the past few decades, a number of studies have tracked the incidence of cancers in IBD patients. Some general trends have been demonstrated:

  • Risk of colorectal cancer has decreased over time in colitis patients, whereas for Crohn’s patients, the change in risk is debatable.
  • The risk of small bowl cancer has not changed over time.
  • The incidence of non-Hodgkin’s lymphoma has increased, more so than Hodgkin’s lymphoma.
  • The incidence of both melanoma and non-melanoma skin cancer has increased over time. This is true for both IBD patients and non-sufferers.

Colorectal cancer (CRC)

CRC is the third most common cancer world-wide, after lung and breast cancer . According to a Danish study of 47,000 IBD patients (here), between 1979-2008 the risk ratio of CRC in patients with ulcerative colitis decreased from 1.34 to 0.57. For Crohn’s patients, no change in the risk ratio was found. A meta-analysis by Castano-Milla (here) also found that the risk of CRC in colitis patients has decreased steadily over the past 6 decades.

A meta-analysis by Canavan et al. (here) measured the risk ratio of CRC in Crohns’ patients over a 30-year period, and found an overall risk ratio reduction of 0.09 per year.

Small bowel cancer

Meta-analyses by Canavan et al. (here) and Laukoetter et al. (here)  failed to demonstrate a  change in the incidence of small bowel cancer over a period of a few decades. Sushil et al. (here) found that, although the incidence of small bowel cancer was higher in Crohn’s patients than non-Crohn’s patients, the ratio remained the same over a 16-year period.

Lymphoma

A number of studies have investigated the incidence of lymphoma in IBD and non-IBD cohorts, but have failed to find a disparity between the two groups.

Sushil et al. (here) found that between 1998-2013:

  • The incidence of non-Hodgkin lymphoma almost doubled in Crohn’s patients discharged from hospital. This change was greater than for the non-Crohn’s patients cohort.
  • The incidence of non-Hodgkin lymphoma also almost doubled in ulcerative colitis patients discharged from hospital.
  • The incidence of Hodgkin lymphoma decreased by 13,000 in Crohn’s patients discharged from hospital.
  • The incidence of Hodgkin lymphoma increased almost 2-fold in colitis patients discharged from hospital.

Extra-intestinal cancers

  • Non-melanoma skin cancer (NMSC)

Sushil et al. (here) found that between 1998-2013, the incidence of NMSC increased  in colitis patients discharged from hospital. A similar trend was noted for patients with Crohn’s disease.  There was a corresponding increase in non-melanoma skin cancer incidence for the non-IBD group, although to a smaller degree.

  • Melanoma

Sushil et al. (here) found that between 1998 and 2013, the incidence of melanoma in colitis patients increased l. For  Crohn’s patients and non-IBD sufferers, the increase was smaller.

Association between drug use and cancer

Immunosuppressant drugs used to IBD are known to increase the risk of lymphoma. A study by Kotlyar et al. (source) demonstrated that there was an increased risk of six-fold  in patients using a particular immunomodulating drug (thiopurine).

A study published by Ariyarthnam et al. (source) demonstrated that patients treated with thiopurines had a risk ratio of 2.28 of developing non-melanoma skin cancer (NMSC). However, a second study by Osterman et al. (source) investigated the effects of another immunomodulator (adalimumab), and did not find a change in the incidence of NMSC.

Although the data are not in complete agreement, there is little evidence that IBD drugs affect the changes of developing melanoma.

 

 * This blog entry is based on the article by Sushil K, published in Curr Opin Gastroenterol. 2016;32(4) – “Risk of Cancer in Inflammatory Bowel Disease: Going up, Going Down, or Still the Same?”

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