Bernstein H, Bernstein C, Payne CM, Dvorak K. Bile acids as endogenous etiologic agents in gastrointestinal cancer. World J Gastroenterol 2009; 15(27): 3329-3340 [PMID: 19610133 DOI: 10.3748/wjg.15.3329]
Corresponding Author of This Article
Katerina Dvorak, PhD, Research Associate Professor, Department of Cell Biology and Anatomy, College of Medicine, and Arizona Cancer Center, University of Arizona, 1501 N. Campbell Avenue, PO Box 245044, Tucson Arizona 85724, United States. kdvorak@email.arizona.edu
Article-Type of This Article
Editorial
Open-Access Policy of This Article
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: http://creativecommons.org/licenses/by-nc/4.0/
World J Gastroenterol. Jul 21, 2009; 15(27): 3329-3340 Published online Jul 21, 2009. doi: 10.3748/wjg.15.3329
Bile acids as endogenous etiologic agents in gastrointestinal cancer
Harris Bernstein, Carol Bernstein, Claire M Payne, Katerina Dvorak
Harris Bernstein, Claire M Payne, Department of Cell Biology and Anatomy, College of Medicine, and Arizona Cancer Center, University of Arizona, Tucson Arizona 85724, United States
Carol Bernstein, Department of Cell Biology and Anatomy, College of Medicine, University of Arizona, Tucson Arizona 85724, United States; Hematology/Oncology Southern Arizona Veterans Affairs Health Care System, Tucson Arizona 85723, United States
Katerina Dvorak, Department of Cell Biology and Anatomy, College of Medicine, and Arizona Cancer Center, University of Arizona, Tucson Arizona 85724, United States; Hematology/Oncology Southern Arizona Veterans Affairs Health Care System, Tucson Arizona 85723, United States
Author contributions: Bernstein H, Bernstein C, Payne CM and Dvorak K contributed equally to this work.
Correspondence to: Katerina Dvorak, PhD, Research Associate Professor, Department of Cell Biology and Anatomy, College of Medicine, and Arizona Cancer Center, University of Arizona, 1501 N. Campbell Avenue, PO Box 245044, Tucson Arizona 85724, United States. kdvorak@email.arizona.edu
Telephone: +1-520-6263934
Fax: +1-520-6262097
Received: May 4, 2009 Revised: June 16, 2009 Accepted: June 23, 2009 Published online: July 21, 2009
Abstract
Bile acids are implicated as etiologic agents in cancer of the gastrointestinal (GI) tract, including cancer of the esophagus, stomach, small intestine, liver, biliary tract, pancreas and colon/rectum. Deleterious effects of bile acid exposure, likely related to carcinogenesis, include: induction of reactive oxygen and reactive nitrogen species; induction of DNA damage; stimulation of mutation; induction of apoptosis in the short term, and selection for apoptosis resistance in the long term. These deleterious effects have, so far, been reported most consistently in relation to esophageal and colorectal cancer, but also to some extent in relation to cancer of other organs. In addition, evidence is reviewed for an association of increased bile acid exposure with cancer risk in human populations, in specific human genetic conditions, and in animal experiments. A model for the role of bile acids in GI carcinogenesis is presented from a Darwinian perspective that offers an explanation for how the observed effects of bile acids on cells contribute to cancer development.
