Chemopreventive effects of 5-aminosalicylic acid on inflammatory bowel disease-associated colorectal cancer and dysplasia: a systematic review with meta-analysis

Abstract

Background and AimsThe chemopreventive effect of 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) has been widely studied; however, the results remain conflicting. The aim of this study was to systematically review the literature and update evidence concerning effects of 5-ASA on the risk of colorectal cancer (CRC) and dysplasia (Dys) in patients with ulcerative colitis (UC) or Crohn's disease (CD).Results5-ASA showed a chemopreventive effect against CRC/Dys in IBD patients (OR = 0.58, 95% CI: 0.45−0.75). However, this effect was significant only in clinical-based studies (OR = 0.51; 95% CI: 0.39−0.65), but not in population-based studies (OR = 0.71; 95% CI: 0.46−1.09). Moreover, this effect was noticeable in patients with UC (OR = 0.46, 95% CI: 0.34−0.61), but not in CD (OR = 0.66, 95% CI: 0.42−1.03), and on the outcome of CRC (OR = 0.54, 95% CI: 0.39−0.74), but not Dys (OR = 0.47; 95% CI: 0.20−1.10). In IBD patients, mesalazine dosage ≥ 1.2 g/day showed greater protective effects against CRC/Dys than dosages < 1.2 g/day. However, Sulphasalazine therapy did not show any noticeable protective function regardless of the dosage administered.Materials and MethodsWe performed a systematic review with a meta-analysis of 26 observational studies involving 15,460 subjects to evaluate the risks of developing CRC and Dys in IBD patients receiving 5-ASA treatment. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each evaluation index.Conclusions5-ASA has a chemopreventive effect on CRC (but not Dys) in IBD patients. Moreover, UC patients can benefit more from 5-ASA than CD patients. Mesalazine maintenance dosage ≥ 1.2 g/day is an effective treatment for reducing CRC risk in IBD patients.

Systematic review with meta‐analysis: high prevalence and cost of continued aminosalicylate use in patients with ulcerative colitis escalated to immunosuppressive and biological therapies

“…In a meta-analysis of 26 observational studies, Bonovas et al reported a 50% reduction in colorectal neoplasia risk among UC patients treated with aminosalicylates (relative risk 0.50, 95% CI 0.38-0.64), an effect that was dose-dependent and primarily driven by mesalamine rather than sulphasalazine. 62 Similar dose-and formulation-dependent conclusions and effect sizes have been reported in second meta-analysis by Qiu et al (OR = 0.46, 95% CI 0.34-0.61) 63.…”

Reactive oxygen species and colorectal cancer

“…Angiogenesis and lymphangiogenesis represent sprouting of new blood and lymphatic vessels from pre-existing ones (Wang et al, 2017).…”

“…The accumulation of ROS triggers autophagy/mitophagy and aerobic glycolysis in CAFs which in turn leads to creation of a lactate-rich microenvironment. In this way, CAFs provide energy and nutrients to cancer cells (Martinez-Outschoorn et al, 2010;Wang et al, 2017). What is more, OuYang et al (2015) recently reported that by inhibiting the product of ROS, the suppression effect myeloid-derived suppressor cells (MDSCs) on T cells proliferation can be abolished, so that inhibiting the growth and metastases of CRC.…”

The protective effect of syringic acid on dextran sulfate sodium‐induced experimental colitis in BALB/c mice

“…Although genetic and environmental factors are assumed to be involved in the pathogenesis of IBD, the fundamental etiology and pathogenesis remain obscure (Chan & Ng, 2017;Silva, Rodrigues, Ayrizono, & Leal, 2016). The pathological events of chronic mucosal inflammation involve inadequate or prolonged activation of the intestinal immune system (Qiu, Ma, Wang, & Zhang, 2017;Yadav et al, 2016). Although evidences suggest that the activation and nuclear translocation of NF-κB partly plays an essential role in the intestinal inflammation.…”