Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022104 (irritable bowel syndrome)
 8,033 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Colorectal cancer (CRC) is still a disease with a high incidence and mortality. Prevention of (pre-) cancerous lesions of CRC by endoscopic screening is promising, but costs are high and identification of high-risk populations is difficult. Since screening both average-risk and high-risk populations for CRC has its logistic and financial limitations, new primary prevention strategies are sought. Substantial evidence has shown that non-steroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors can reduce the incidence and mortality of CRC. However, long-term use of NSAIDs is associated with substantial gastrointestinal toxicity and may cause an exacerbation in IBD patients. Selective COX-2 inhibitors, with a better toxicity profile and no flare-up in IBD disease activity, are therefore attractive candidates for prevention. Chemoprevention with low-dose aspirin can be considered for individuals carrying a high risk for CRC. Folate supplementation is beneficial to the folate-depleted patients, since significant risk reductions for CRC are reported. Moreover, it might be applicable to the general population because it is safe, inexpensive and protects against vascular diseases. In line with drugs beneficial for multiple disease entities, statins have recently been proposed to reduce CRC risk. Ursodeoxycholic acid has been shown to decrease the incidence of colonic dysplasia in patients with ulcerative colitis and PSC and possibly reduces recurrence rates of polyps in general. Unfortunately, prospective randomized trials, in both high-risk and general population, are not available and the evidence is still controversial. Furthermore, cumulative epidemiological and observational data suggest the potential role of hormones as a chemoprotective agent. An increase in CRC in females with an early menopause, as well as a decrease of CRC in women with hormone replacement therapy justify further research into this issue. In IBD patients, both the severity and duration of the inflammation are the most evident risk factors for the development of dysplasia and subsequently cancer. Remission of inflammation, clinically, endoscopically and histologically, in IBD is the major goal. Long-term use of 5-aminosalicylates (5-ASA) has been shown to decrease the incidence of CRC and may hold the best promise as a chemoprotective agent in IBD. In parallel with primary prevention strategies in vascular medicine, the aim might be to postpone adenoma formation, for instance for 10 years, thereby achieving a significant risk reduction for CRC. In current practice, folate supplementation along with low-dose aspirin use in high-risk patients may be most attractive candidates, while future studies will have to clarify the role of these and other chemoprotective agents.
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PMID:Chemoprevention for colon cancer: new opportunities, fact or fiction? 1678 36

The ideal chemopreventative agent, in addition to being efficacious in the prevention of cancer, must be easily administered, affordable, safe, and well tolerated, with minimal side effects. In the past decade, a growing body of literature has emerged on the prevention of CRC in patients with long-standing CD and UC. The data are not definitive and consist almost exclusively of retrospective case-control and cohort studies rather than the more rigorous prospective RCTs. 5-ASA compounds have been most thoroughly studied, and most of the existing data support the use of 5-ASA in the prevention of CRC. Although the precise dose and duration are unclear, studies suggest that chronic systemic administration of 5-ASA at a dose of at least 1.2 g/d is most likely to be effective. A beneficial effect of folate, albeit not statistically significant, has been consistently shown in every study performed for this purpose. Folate supplementation, which is safe and affordable, should also be recommended for all patients with IBD, especially those taking sulfasalazine. UDCA has been shown to exert a protective effect in most studies on patients with UC and concomitant PSC. Because this patient population is at particularly high risk for CRC, it is advisable to consider UDCA in all patients with colitis complicated by PSC. For patients without PSC, sufficient data do not exist to recommend it for the purpose of cancer prevention. Five of the six corticosteroid studies have found a beneficial effect of systemic steroids, although most did not reach statistical significance. Regardless, given the frequent and serious adverse effects associated with chronic steroid use, systemic corticosteroids should not be prescribed for this indication. Budesonide, an oral corticosteroid with minimal systemic absorption, is a potential alternative, although it has not yet been studied as a chemopreventative agent. Similarly, until the long-term safety of chronic NSAID use can be demonstrated in patients with IBD, the role of NSAIDs in chemoprevention remains undefined. Although the data are conflicting, immune-modulating medications, such as AZA, do not seem to confer any reduction in the risk of dysplasia or CRC. The data on calcium supplementation and statin use are still too limited to endorse their use for the prevention of colitis-related CRC. Chemoprevention is an area that holds great promise in the reduction of morbidity and mortality associated with IBD. Further studies, including prospective trials when possible and cost-effectiveness analyses, need to be performed to develop an optimal strategy for the reduction of cancer risk in patients with IBD.
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PMID:Chemoprevention: risk reduction with medical therapy of inflammatory bowel disease. 1695 46