Copyright ©The Author(s) 2016. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2016; 22(33): 7463-7477
Published online Sep 7, 2016. doi: 10.3748/wjg.v22.i33.7463
Role of bile acids in carcinogenesis of pancreatic cancer: An old topic with new perspective
Hui-Yi Feng, Yang-Chao Chen
Hui-Yi Feng, Yang-Chao Chen, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Hong Kong, China
Author contributions: Feng HY and Chen YC wrote the paper.
Supported by General Research Fund, Research Grants Council of Hong Kong, No. CUHK462211, No. CUHK462713 and No. 14102714; National Natural Science Foundation of China, No. 81101888 and No. 8142730; and Direct Grant from CUHK.
Conflict-of-interest statement: No conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Yang-Chao Chen, PhD, School of Biomedical Sciences, Faculty of Medicine, the Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Telephone: +852-39431100 Fax: +852-26035123
Received: April 9, 2016
Peer-review started: April 10, 2016
First decision: May 12, 2016
Revised: June 30, 2016
Accepted: July 20, 2016
Article in press: July 20, 2016
Published online: September 7, 2016

The role of bile acids in colorectal cancer has been well documented, but their role in pancreatic cancer remains unclear. In this review, we examined the risk factors of pancreatic cancer. We found that bile acids are associated with most of these factors. Alcohol intake, smoking, and a high-fat diet all lead to high secretion of bile acids, and bile acid metabolic dysfunction is a causal factor of gallstones. An increase in secretion of bile acids, in addition to a long common channel, may result in bile acid reflux into the pancreatic duct and to the epithelial cells or acinar cells, from which pancreatic adenocarcinoma is derived. The final pathophysiological process is pancreatitis, which promotes dedifferentiation of acinar cells into progenitor duct-like cells. Interestingly, bile acids act as regulatory molecules in metabolism, affecting adipose tissue distribution, insulin sensitivity and triglyceride metabolism. As a result, bile acids are associated with three risk factors of pancreatic cancer: obesity, diabetes and hypertriglyceridemia. In the second part of this review, we summarize several studies showing that bile acids act as cancer promoters in gastrointestinal cancer. However, more question are raised than have been solved, and further oncological and physiological experiments are needed to confirm the role of bile acids in pancreatic cancer carcinogenesis.

Keywords: Bile acids, Pancreatic adenocarcinoma, Pancreatitis, Metabolic syndrome

Core tip: Bile acids bridge the gap between risk factors and pancreatic cancer, providing a new horizon in pancreatic cancer carcinogenesis.