Bile Acid and Colorectal Cancer

Fig. 14.1
The schema of the randomized control study [36]. Eligible criteria included the removal of one or more colorectal adenomas with a diameter of 3 mm or more during a colonoscopy examination within 6 months before study registration. Of 6570 potential participants, 1537 were eligible for randomized. Of these 1537 participants, 252 were excluded for various reasons. Of these, a total of 1192 underwent at least one colorectal evaluation 6 months of more after randomization and were evaluable for outcome. Finally, 579 in the placebo group and 613 in the UDCA group were analyzed. The primary outcome of this phase III study was the recurrence of colorectal adenomas in 3 years. The results indicated that a nonstatically significant (P = 0.15) 12% reduction in the adenoma recurrence rate is associated with UDCA intervention (rate ratio = 0.88, 95% confidence interval (CI) = 0.37–1.05). However, a statistically significant (P = 0.03) UDCA related reduction in recurrence of adenoma with high-grade dysplasia (adjusted OR = 0.61, 95% CI = 0.39–0.96).

The UDCA effects were investigated in patients with inflammatory bowel disease (IBD) with primary biliary cirrhosis (PBC). The first study was a retrospective analysis of risk factors for dysplasia in 59 patients with UC-associated PBC. On multivariate analysis, UDCA was negatively associated with the risk of colonic dysplasia.

In the patients with familial adenomatous polyposis (FAP), duodenal adenomas are observed in approximately 90%. Some studies suggest that bile acids may play a role in the development of duodenal adenomas. Therefore, 71 patients with FAP and restorative proctocolectomy were randomized to receive UDCA or a placebo for 2 years. The results indicated that nine (25%) patients in the UDCA group and seven (20%) in the placebo group had a decrease in Spiegelman’s score (p = 0.614), suggesting that UDCA had no significant effect on the severity of duodenal adenomas in FAP patients [45].

14.4 Future Perspective

In this review, we summarized the two biological effects of the bile acids. The bile acids can induce cellular stresses, oxidative DNA damage, and mitochondrial damage in the epithelial cells in the GI tract. Persistent exposure of the bile acids can result in the development of apoptosis resistant and the modulation of many genes/proteins associated with colorectal carcinogenesis. On the other hand, chemoprevention effect of UDCA has been shown in several clinical studies; however, the efficacy of the UDCA is still under debate. Further basic research into bile acids may provide the new therapy for the CRC.



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Sep 30, 2017 | Posted by in GASTROENTEROLOGY | Comments Off on Bile Acid and Colorectal Cancer

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