Chemoprevention of colorectal neoplasia in ulcerative colitis: the effect of 6-mercaptopurine.
OBJECTIVE
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.
Matula
Sierra
S
Dr. Henry D. Janowitz Division of Gastroenterology, Department of Medicine, Mount Sinai School of Medicine, New York, New York 10029, USA.
Croog
Victoria
V
Itzkowitz
Steven
S
Harpaz
Noam
N
Bodian
Carol
C
Hossain
Sabera
S
Ullman
Thomas
T
D000328:Adult; D001379:Azathioprine / Q000627:therapeutic use; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D003093:Colitis, Ulcerative / Q000150:complications / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000517:prevention & control*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D015122:Mercaptopurine / Q000627:therapeutic use*; D016016:Proportional Hazards Models
D007166:Immunosuppressive Agents; D015122:Mercaptopurine; D001379:Azathioprine