2003Alimentary Pharmacology & TherapeuticsOpen access

Review article: the data supporting a role for aminosalicylates in the chemoprevention of colorectal cancer in patients with inflammatory bowel disease

Jayne Eaden

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Abstract

The chemoprevention of colorectal cancer (CRC) with long-term sulfasalazine and 5-aminosalicyclic acid (5-ASA) treatment has been demonstrated through epidemiological and experimental studies, in patients with ulcerative colitis. In a large case-controlled study, there was a trend for long-term nonsteroidal anti-inflammatory consumption to be protective against CRC in patients with inflammatory bowel disease (IBD) (OR, 0.84). Sulfasalazine treatment over a 3-month period was shown to be protective (OR, 0.38), independently of disease activity. A longer-term study of sulfasalazine also revealed a relationship with treatment compliance, where 3% of compliant patients developed CRC compared with 31% of the noncompliers. Treatment with 5-ASA was associated with an increase in apoptosis, a decrease in proliferation of colorectal mucosa and has been shown to lower the rate of spontaneous mutation. In a retrospective, matched case-control study conducted in the UK, 102 patients with ulcerative colitis and CRC were matched with ulcerative colitis patients without CRC. Incidence was correlated to treatment protocols, family history and other risk factors. Mesalazine was the only treatment to be associated with a statistically significant reduction in the risk of developing cancer. Even after adjusting for variables, mesalazine at doses > 1.2 g / day reduced the risk of cancer by 81% (P = 0.006). Frequent visits to the clinician were also associated with a protective effect.

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The chemoprevention of colorectal cancer (CRC) with long-term sulfasalazine and 5-aminosalicyclic acid (5-ASA) treatment has been demonstrated through epidemiological and experimental studies, in patients with ulcerative colitis. In a large case-controlled study, there was a trend for long-term nonsteroidal anti-inflammatory consumption to be protective against CRC in patients with inflammatory bowel disease (IBD) (OR, 0.84). Sulfasalazine treatment over a 3-month period was shown to be protective (OR, 0.38), independently of disease activity. A longer-term study of sulfasalazine also revealed a relationship with treatment compliance, where 3% of compliant patients developed CRC compared with 31% of the noncompliers. Treatment with 5-ASA was associated with an increase in apoptosis, a decrease in proliferation of colorectal mucosa and has been shown to lower the rate of spontaneous mutation. In a retrospective, matched case-control study conducted in the UK, 102 patients with ulcerative colitis and CRC were matched with ulcerative colitis patients without CRC. Incidence was correlated to treatment protocols, family history and other risk factors. Mesalazine was the only treatment to be associated with a statistically significant reduction in the risk of developing cancer. Even after adjusting for variables, mesalazine at doses > 1.2 g / day reduced the risk of cancer by 81% (P = 0.006). Frequent visits to the clinician were also associated with a protective effect.

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Available abstract

The chemoprevention of colorectal cancer (CRC) with long-term sulfasalazine and 5-aminosalicyclic acid (5-ASA) treatment has been demonstrated through epidemiological and experimental studies, in patients with ulcerative colitis. In a large case-controlled study, there was a trend for long-term nonsteroidal anti-inflammatory consumption to be protective against CRC in patients with inflammatory bowel disease (IBD) (OR, 0.84). Sulfasalazine treatment over a 3-month period was shown to be protective (OR, 0.38), independently of disease activity. A longer-term study of sulfasalazine also revealed a relationship with treatment compliance, where 3% of compliant patients developed CRC compared with 31% of the noncompliers. Treatment with 5-ASA was associated with an increase in apoptosis, a decrease in proliferation of colorectal mucosa and has been shown to lower the rate of spontaneous mutation. In a retrospective, matched case-control study conducted in the UK, 102 patients with ulcerative colitis and CRC were matched with ulcerative colitis patients without CRC. Incidence was correlated to treatment protocols, family history and other risk factors. Mesalazine was the only treatment to be associated with a statistically significant reduction in the risk of developing cancer. Even after adjusting for variables, mesalazine at doses > 1.2 g / day reduced the risk of cancer by 81% (P = 0.006). Frequent visits to the clinician were also associated with a protective effect.

Key concepts: Medicine, Sulfasalazine, Mesalazine, Ulcerative colitis, Inflammatory bowel disease, Internal medicine, Gastroenterology, Colorectal cancer

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