Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine

Clin Gastroenterol Hepatol. 2005 Oct;3(10):1015-21. doi: 10.1016/s1542-3565(05)00738-x.


Background & aims: Evidence suggests that mesalamine-based anti-inflammatory medicines may prevent colorectal cancer (CRC) in ulcerative colitis (UC). If mesalamine exerts its chemopreventive effect by its anti-inflammatory activity, then other medications that reduce colitis activity also should possess chemopreventive properties. Our aim was to determine the effect of the immunomodulators 6-mercaptopurine (6MP) and azathioprine (AZA) in preventing the development of dysplasia or CRC in UC.

Methods: Patients with UC who underwent a surveillance colonoscopy in 1996-1997 were identified from a gastrointestinal pathology database. A proportional hazards analysis assessing 6MP/AZA use as a time-changing covariate was performed to evaluate the effect of 6MP/AZA on: (1) progression to any neoplasia (low-grade dysplasia, high-grade dysplasia, or CRC), and (2) progression to advanced neoplasia (high-grade dysplasia or CRC).

Results: A total of 315 subjects met inclusion criteria and were followed for an average of 8 years from their first surveillance examination. There were no significant differences in rates of progression to advanced neoplasia or to any neoplasia between 6MP/AZA users and never-users by log-rank testing. The proportional hazards analysis resulted in hazard ratios of 1.06 (95% confidence interval, .59-1.93) and 1.30 (95% confidence interval, .45-3.75) when considering the effect of exposure to 6MP/AZA on progression to any or to advanced neoplasia, respectively. The results were unaffected by known potential confounders.

Conclusions: In UC patients with no initial history of dysplasia, 6MP/AZA use appears to have little or no effect on the rate of neoplastic transformation in the colon. Importantly, the use of 6MP/AZA did not increase malignant transformation in UC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Azathioprine / therapeutic use
  • Cell Transformation, Neoplastic / drug effects
  • Colitis, Ulcerative / complications
  • Colitis, Ulcerative / drug therapy*
  • Colorectal Neoplasms / prevention & control*
  • Disease Progression
  • Female
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Male
  • Mercaptopurine / therapeutic use*
  • Proportional Hazards Models


  • Immunosuppressive Agents
  • Mercaptopurine
  • Azathioprine