The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) has been acknowledged for almost a century and is assumedly promoted by a chronic inflammation-driven carcinogenic process in the intestine in combination with a genetic predisposition. The magnitude of the risk of CRC in IBD remains a continuing subject of debate. The early, high risk estimates for CRC in IBD were most likely overestimated due to selected patient populations originating from tertiary referral centers with a disproportional high percentage of patients with severe disease. Later population-based studies calculating risk estimates from a broad spectrum of IBD patients have found the risk to be significantly lower. At present, there is evidence that IBD patients with longstanding and extensive disease with uncontrolled inflammation are those at increased risk. Additional, other recognized risk factors include early age at onset, family history of CRC, and concomitant primary sclerosing cholangitis. A significant amount of effort is put into identifying potential preventive factors of CRC in IBD, including surveillance programs and chemopreventive agents but the individual effect of these remains uncertain. Interestingly, recent studies have reported a decline in risk of CRC over time. Surveillance programs and the new treatment strategies, particular biological treatment might be part of the reason for the observed decline in risk of CRC in IBD over time but future studies will have investigate this assumption.
"The link between chronic intestinal inflammation and CRC risk is known . Previous preclinical evidence using an animal model of ulcerative colitis described the antiinflammatory activity of Uro-A , the most significant urolithin produced by humans . "
[Show abstract][Hide abstract] ABSTRACT: Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from colorectal cancer (CRC) patients after pomegranate extract (PE) intake.
CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin:EA ratio were administered. Twenty-three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 ± 367 ng/g) was found in NT after consumption of PE-1 and the lowest concentration (42.4 ± 10.2 ng/g) in MT with PE-2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE-2) hampered urolithins formation.
Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.
"Finally, CRC may develop in an inflammatory background resulting from severe and chronic activity in inflammatory bowel disease (Crohn's disease or ulcerative colitis). Contrary to the early reports of a very high cancer risk in these patients, primarily populations with severe disease investigated in tertiary referral centers, many later epidemiological follow-up studies have demonstrated only a moderately increased risk of cancer development , which is likely greater for Crohn's disease than ulcerative colitis . However, compared with sporadic or hereditary CRC, risk is increased, and the mechanisms appear to be different. "
[Show abstract][Hide abstract] ABSTRACT: The interconnectivity between diet, gut microbiota and cell molecular responses is well known; however, only recently has technology allowed the identification of strains of microorganisms harbored in the gastrointestinal tract that may increase susceptibility to cancer. The colonic environment appears to play a role in the development of colon cancer, which is influenced by the human metabolic lifestyle and changes in the gut microbiome. Studying metabolic changes at the cellular level in cancer be useful for developing novel improved preventative measures, such as screening through metabolic breath-tests or treatment options that directly affect the metabolic pathways responsible for the carcinogenicity.
Cancer letters 03/2014; 356(2). DOI:10.1016/j.canlet.2014.02.026 · 5.62 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Neoplasia complicating ulcerative colitis (UC-neoplasia) is a problem that is poorly addressed by present surveillance techniques. The association of greater than 300 single nucleotide polymorphisms (SNPs) with inflammatory bowel disease (IBD) suggests the possibility that certain genetic polymorphisms might identify patients with UC destined for malignant degeneration. This present study tested the hypothesis that presently known IBD-associated SNPs may correlate with UC-neoplasia.
Materials and methods:
A total of 41 patients with UC-neoplasia (mean age 56 ± 2.1 years) were identified from our divisional IBD Biobank (low-grade dysplasia n = 13, high-grade dysplasia n = 8, colorectal cancer [CRC] n = 20). These patients were individually age, sex, and disease duration matched with UC patients without neoplasia. Primary sclerosing cholangitis and family history of CRC were recorded. Patients were genotyped for 314 of the most commonly IBD-associated SNPs by a custom SNP microarray. Logistic regression and Fischer exact test were used for statistical analysis.
After Bonferroni correction, none of the 314 IBD-associated SNPs correlated with UC-neoplasia when compared with matched UC controls. The incidence of primary sclerosing cholangitis was greater in the UC-neoplasia group (10/41, 24% vs 3/41, 7%; P = .03) compared with UC controls. The severity of neoplasia (low grade dysplasia versus high grade dysplasia versus CRC) correlated with disease duration (7.9 vs 13.4 vs 20.7 years, respectively).
The lack of correlation between well-known IBD-associated SNPs and UC-neoplasia demonstrated in this study suggests that the development of neoplasia in patients with UC is associated with genetic determinants other than those that predispose to inflammation or results from posttranslational modifications or epigenetic factors rather than germline polymorphisms.
Surgery 03/2014; 156(2). DOI:10.1016/j.surg.2014.03.017 · 3.38 Impact Factor
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