Review article: malignancy on thiopurine treatment with special reference to inflammatory bowel disease.
BACKGROUND
Immunosuppression is a risk factor for carcinogenesis. Thiopurines specifically contribute to this. As thiopurines are used more aggressively in the treatment of IBD, it is likely that we will see more thiopurine-related malignancy.


OBJECTIVE
To review the literature, exploring how immunosuppression, thiopurines specifically, might cause cancer and which malignancies occur in practice, placing specific emphasis on IBD cohorts.


METHODS
Search terms included 'malignancy' 'cancer' 'azathioprine' 'mercaptopurine' 'tioguanine (thioguanine)' 'thiopurine' and 'inflammatory bowel disease' 'Crohn's disease' 'ulcerative colitis'. We also searched for specific cancers (lymphoma, colorectal cancer, skin cancer, cervical cancer) and reviewed the reference lists of the articles detected.


RESULTS
Immunosuppression is associated with an increased risk of cancer. Thiopurines are associated with specific additional risks. In IBD cohorts, very few thiopurine-related malignancies have been reported. However, studies suggest a relative risk of 4-5 for lymphoma. This still translates into a low actual risk, (one extra lymphoma in every 300-1400 years of thiopurine treatment).


CONCLUSIONS
Whilst we must be aware of this risk and counsel our patients appropriately, thiopurines remain a mainstay of IBD therapy. We present practical advice aimed at minimizing our patients' risk of developing malignancy, whilst optimizing the benefits that thiopurines can provide.
Smith
M A
MA
Department of Gastroenterology Guy's & St. Thomas' NHS Foundation Trust, London, UK.
Irving
P M
PM
Marinaki
A M
AM
Sanderson
J D
JD
D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D009369:Neoplasms / Q000139:chemically induced*; D010353:Patient Education as Topic; D017410:Practice Guidelines as Topic; D010818:Practice Patterns, Physicians'; D011687:Purines / Q000009:adverse effects*; D012307:Risk Factors; D013872:Thionucleosides / Q000009:adverse effects*
D007166:Immunosuppressive Agents; D011687:Purines; D013872:Thionucleosides