Cited by 340Cholangiocarcinoma and Gallbladder Cancer StudiesCarcinogens and Genotoxicity AssessmentEsophageal Cancer Research and Treatment

Bile acids as endogenous etiologic agents in gastrointestinal cancer

Open access
Bernstein, Harris, Bernstein, Carol, Payne, Claire M, Dvorak, Katerina·2009·World Journal of Gastroenterology

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.

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  • Secondary bile acids may contribute to colorectal cancer development by generating reactive oxygen and nitrogen species that damage DNA and promote apoptosis resistance.

    “Secondary bile acids might contribute to development of CRC because they generate reactive oxygen and nitrogen species that cause DNA damage and promote resistance to apoptosis.160”

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  1. Mahmoud NN, Dannenberg AJ, Bilinski RT, Mestre JR, Chadburn A, Churchill M, Martucci C, Bertagnolli M M . A d m i n i s t r a t i o n o f a n u n c o n j u g a t e d b i l e a c i d increases duodenal tumors in a murine model of familial adenomatous polyposis. Carcinogenesis 1999; 20: 299-303
  2. Reddy BS, Hedges AR, Laakso K, Wynder EL. Metabolic epidemiology of large bowel cancer: fecal bulk and constituents of high-risk North American and low-risk Finnish population. Cancer 1978; 42: 2832-2838 106
  3. Plesca D, Mazumder S, Almasan A. DNA damage response and apoptosis. Methods Enzymol 2008; 446: 107-122 163

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Authors
Bernstein, H., Bernstein, C., Payne, C. M., & Dvorak, K.
Affiliations
Atrium Health Wake Forest Baptist (US)
Corresponding author
Dvorak, Katerina
Venue
World Journal of Gastroenterology
Published
2009
Volume
15
Issue
27
Pages
3329
ISSN
1007-9327 (ISSN-L)
OpenAlex
W2160363801
Cited by
340
References
174
Citations by year
2026: 18 · 2025: 30 · 2024: 23 · 2023: 27 · 2022: 29 · 2021: 25 · 2020: 13 · 2019: 16 · 2018: 32 · 2017: 13 · 2016: 16 · 2015: 16 · 2014: 20 · 2013: 19 · 2012: 13
FWCI
14.19
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • World Journal of Gastroenterology (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Arizona Biomedical Research Commission
  • National Institutes of Health (5r21ca111513-02)
  • National Cancer Institute (R01CA119087, R21 CA111513, 1P50 CA 95060, R21CA111513-01A1, P50CA095060)
Topics
  • Health Sciences › Medicine › Surgery › Cholangiocarcinoma and Gallbladder Cancer Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
  • Health Sciences › Medicine › Surgery › Esophageal Cancer Research and Treatment
Keywords
bile acids, gastrointestinal cancer, carcinogenesis, esophageal cancer, colorectal cancer, reactive oxygen species, reactive nitrogen species, DNA damage, apoptosis, apoptosis resistance, cancer risk
MeSH terms
Animals, Bile Acids and Salts, Carcinogens, Cell Transformation, Neoplastic, DNA Damage, Female, Gastrointestinal Neoplasms, Humans, Male, Risk Factors, Apoptosis, Reactive Oxygen Species, Receptors, Cytoplasmic and Nuclear

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