Long-term therapy with sulphasalazine protects against colorectal cancer in ulcerative colitis: a retrospective study of colorectal cancer risk and compliance with treatment in Leicestershire

Moody, G. A.; Venkataraman, Jayanthi; Probert, Chris; Kay, H. Mac; Mayberry, J. F.

doi:10.1097/00042737-199612000-00009

Cited by 221 publications

(148 citation statements)

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“…These results together with our cytokine data strongly suggest that the anti-inflammatory properties of HDAC inhibitors in models of inflammatory bowel disease depend on the suppression of proinflammatory cytokines as well as the induction of apoptosis. For patients with chronic inflammatory bowel diseases, ulcerative colitis more than Crohn's disease is associated with an increased risk of colon cancer (29,30). HDAC inhibitors have primarily been investigated and developed for cancer therapy, and are currently tested in clinical trials for a variety of solid and hemological cancers (4).…”

Section: Discussionmentioning

confidence: 99%

Histone Hyperacetylation Is Associated with Amelioration of Experimental Colitis in Mice

Glauben

Batra

Fedke

et al. 2006

The Journal of Immunology

270

190

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Inhibitors of histone deacetylases (HDAC) are being studied for their antiproliferative effects in preclinical cancer trials. Recent studies suggest an anti-inflammatory role for this class of compounds. Because inflammatory bowel disease is associated with an increased risk of malignancies, agents with antiproliferative and anti-inflammatory properties would be of therapeutic interest. HDAC inhibitors from various classes were selected and evaluated for their in vitro capacity to suppress cytokine production and to induce apoptosis and histone acetylation. Valproic acid (VPA) and suberyolanilide hydroxamic acid (SAHA) were chosen for further studies in dextran sulfate sodium- and trinitrobenzene sulfonic acid-induced colitis in mice. In vitro, inhibition of HDAC resulted in a dose-dependent suppression of cytokine synthesis and apoptosis induction requiring higher concentrations of HDAC inhibitors for apoptosis induction compared with cytokine inhibition. Oral administration of either VPA or SAHA reduced disease severity in dextran sulfate sodium-induced colitis. The macroscopic and histologic reduction of disease severity was associated with a marked suppression of colonic proinflammatory cytokines. In parallel to the beneficial effect observed, a dose-dependent increase in histone 3 acetylation at the site of inflammation was shown under VPA treatment. Furthermore, SAHA as well as VPA treatment resulted in amelioration of trinitrobenzene sulfonic acid-induced colitis, which was associated with an increase of apoptosis of lamina propria lymphocytes. Inhibitors of HDAC reveal strong protective effects in different models of experimental colitis by inducing apoptosis and suppressing proinflammatory cytokines, thereby representing a promising class of compounds for clinical studies in human inflammatory bowel disease.

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Section: Discussionmentioning

confidence: 99%

Histone Hyperacetylation Is Associated with Amelioration of Experimental Colitis in Mice

Glauben

Batra

Fedke

et al. 2006

The Journal of Immunology

270

190

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“…www.wjgnet.com Pinczowski et al [31] Case-control 298 Sulfasalazine > 3 mo OR CRC : 0.38 (95% CI, 0.2-0.69) patients administered sulfasalazine Moody et al [101] Case-control 175 Sulfasalazine < 6 mo 10-fold elevated risk in non-exposed patients (30% vs 3%) Eaden et al [40] Case-control 102 Sulfasalazine, mesalasine regular use OR CRC : 0.25 (95% CI, 0.13-0.48) in regular users Lindberg et al [102] Cohort study 143 Sulfasalazine > 6 mo Non-significant decrease of risk (34% vs 44%) Bernstein et al [87] Case-control 373 5-ASA Non-significant elevation of risk in patients exposed Rutter et al [29] Case-control 204 5-ASA Non-significant elevation of risk of dysplasia in patients exposed Rubin et al [90] Case-control 124 5-ASA > 1.2 g regular use OR CRC : 0.28 (95% CI, 0.09-0.85) in regular users the use of any 5-ASA compound was associated with a 75% decreased risk of CRC (95% CI, 0.13-0.48). Among all 5-ASA compounds, mesalamine use was associated with the greatest degree of protection, providing the most benefit at doses greater than 1.2 g/d (OR, 0.09; 95% CI, 0.03-0.28).…”

Section: Chemoprevention In Ibd-is It Possible?mentioning

confidence: 99%

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

Lakatos¹,

Lakatos²

2008

WJG

373

245

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Since the first report of an inflammatory bowel disease (IBD) case associated with colorectal cancer (CRC) by Crohn and Rosenberg [1] , significant efforts have been made to elucidate this presumed association. Nowadays, the association between IBD and the increased risk for CRC is widely accepted. Although CRC, complicating ulcerative colitis and Crohn's disease, accounts only for 1%-2% of all cases of CRC in the general population, it is considered a serious complication of the disease and accounts for approximately 10%-15% of all deaths in IBD patients [2] . The age at diagnosis of CRC associated with IBD is 15-20 years earlier compared to sporadic cancers. In the meta-analysis by Eaden et al [3] , the average age at diagnosis was 43.2 years. Similarly, in a recent publication from Eastern Europe [4] , it was found to be 50.9 years, 10-15 years younger compared to sporadic CRC cases from the same area (62.2 years) [5] . According to US [6] and Canadian [7] publications, almost two-thirds of the affected patients were males, yet results are conflicting [4,8] . In addition, the frequency of multiple CRCs is higher than in patients with sporadic CRC [9] .The increased risk of CRC in UC is almost a universal finding [3,[10][11][12][13] , yet the extent of this risk varies considerably with differences in study design and geographic area. The initial reports were published by tertiary gastroenterology centers, thus the high risk detected might have been a consequence of referral bias and overinterpretation due to the high percentage of extensive and chronically active cases in these cohorts. Results of population-based studies are more reliable; however, several geographical and ethnic differences have been noted.The report of the meta-analysis by Eaden et al [3] in 2001 was one of several milestones in this subject. The incidence of UC-associated CRC was estimated based on 116 articles involving 54 478 patients in whom 1698 CRC cases were detected. This was a mixture of referral center-based, hospital-based, and population-based studies of variable methodological qualities and levels of detail. The reported incidence was higher in the US AbstractThe risk of colorectal cancer for any patient with ulcerative colitis is known to be elevated, and is estimated to be 2% after 10 years, 8% after 20 years and 18% after 30 years of disease. Risk factors for cancer include extent and duration of ulcerative colitis, primary sclerosing cholangitis, a family history of sporadic colorectal cancer, severity of histologic bowel inflammation, and in some studies, young age at onset of colitis. In this review, the authors discuss recent epidemiological trends and causes for the observed changes. Population-based studies published within the past 5 years suggest that this risk has decreased over time, despite the low frequency of colectomies. The crude annual incidence rate of colorectal cancer in ulcerative colitis ranges from approximately 0.06% to 0.16% with a relative risk of 1.0-2.75. The exact mechanism for this chang...

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“…They found an independent chemoprotective effect for sulfasalazine taken for at least 3 months with an odds ratio of 0.38 (95% CI: 0.2-0.69 after adjusting for disease activity) (Pinczowski et al, 1994). In an other retrospective study by Moody et al, the crude proportion of UC patients developing CAC was of 3% in those taking long-term 5-ASA compared to 31% in those who stopped their treatment or had poor compliance with 5-ASA therapy (χ 2 = 20.2, P < 0.001) (Moody et al, 1996). Several years later, Eaden et al confirmed these findings in a retrospective case-control study: in UC patients, continuous treatment (defined as a treatment for 5 to 10 years) with 5-ASA reduced the CAC risk, at least by 75% [Odds ratio (OR): 0.75, 95% CI: 0.13-0.48] (Eaden et al, 2000).…”

Section: Clinical Datamentioning

confidence: 96%

Ulcerative Colitis-Associated Colorectal Cancer Prevention by 5-Aminosalicylates: Current Status and Perspectives

Reimund¹,

Tavernier²,

Viennot³

et al. 2012

Ulcerative Colitis From Genetics to Complications

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Ulcerative Colitis from Genetics to Complications 150 hypothesis have emerged, resulting from fundamental research in molecular biology and pharmacology. This increased understanding of the putative pathway(s) by which 5-ASA may interfere with CAC development appears also as the starting point for optimising 5-ASA derivatives or identifying new compounds acting more specifically and/or being more efficient in preventing neoplastic transformation of the colonic epithelium in UC patients. These different points will be addressed more precisely in the three next parts. Frequency of colorectal cancer risk in ulcerative colitis and risk factors

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Long-term therapy with sulphasalazine protects against colorectal cancer in ulcerative colitis: a retrospective study of colorectal cancer risk and compliance with treatment in Leicestershire

Cited by 221 publications

References 0 publications

Histone Hyperacetylation Is Associated with Amelioration of Experimental Colitis in Mice

Histone Hyperacetylation Is Associated with Amelioration of Experimental Colitis in Mice

Risk for colorectal cancer in ulcerative colitis: Changes, causes and management strategies

Ulcerative Colitis-Associated Colorectal Cancer Prevention by 5-Aminosalicylates: Current Status and Perspectives

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