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Topic: Reviews of Recent Advances in Research and Treatment for
Gastroenterological Malignancies

Chronic infl ammation and gastrointestinal cancer

1,2
Satoshi Ida , Masayuki Watanabe , Hideo Baba 2
1
1 Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan.
2 Department of Gastroenterological Surgery, Graduate School of Medical Sciences, Kumamoto University, Kumamoto 860-8556, Japan.
Correspondence to: Dr. Masayuki Watanabe, Department of Gastroenterological Surgery, Cancer Institute Hospital of Japanese Foundation for
Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo 135-8550, Japan. E-mail: masayuki.watanabe@jfcr.or.jp

ABSTRACT
Chronic infl ammation has been identifi ed as an important risk factor in the development of the gastrointestinal (GI) tract cancers,
and the underlying molecular mechanisms have been studied extensively. Chronic infl ammation is able to trigger cellular
events to promote malignant transformation of normal epithelial cells in the GI tract to cancer. Host infl ammation responses in
carcinogenesis are through multiple mechanisms such as reactive oxygen and nitration species from mononuclear phagocytes
and leukocytes, immune response and pro-infl ammatory cytokines. Nuclear factor-κB (NF-κB) has been considered as the
central mediator of the immune response. Activation of NF-κB by phosphorylation leads to translocation of NF-κB protein to
the nucleus, and in turn regulates the transcription of several pro-infl ammatory cytokines and chemokines. Furthermore, chronic
infl ammation creates an environment for genomic and epigenetic changes. In this review, we summarize the important molecular
mechanisms that link chronic infl ammation and GI tract cancer, including esophageal, gastric and colonic cancers, focusing on
infective and noninfective agents such as gastroesophageal refl ux disease, Helicobacter pylori gastritis and infl ammatory bowel
disease.
Key words: Cancer, gastrointestinal tract, immune response, infl ammation

Introduction Some of these, such as alcohol and acid, can cause GI
cancers by linking to chronic infl ammation [Table 1]. [2,3]
It is now widely accepted that inadequately resolved Thus, in this review, we discussed emerging concepts
chronic infl ammation could increase cancer risk. The
etiology of infl ammation varies and could result from and provided specifi c examples for the role of chronic
infection with viruses, bacteria or parasites. Alternatively, infl ammation in the development of GI cancers, including
it may be noninfective but caused by a physical or esophageal, gastric and colonic cancers, since they have
chemical irritant. For example, hepatitis B and C viruses been investigated most thoroughly.
account for more than 80% of hepatocellular carcinoma Role of Chronic Infl ammation in Cancer
cases in the world, while human papillomavirus Development
infection is the leading cause of anogenital cancer,
and Helicobacter pylori has been considered as the Immune response and cytokines in cancers
major cause of gastric adenocarcinoma and is known to
signifi cantly increase the risk of gastric mucosa-associated Chronic infl ammation is characterized by the infi ltration
lymphoid tissue lymphoma. Moreover, there are numerous of mononuclear cells, such as macrophages, lymphocytes
examples of noninfective agents being associated with and plasma cells in damaged tissue, together with tissue
infl ammation and development of cancers. Several destruction and attempts to repair. In this infl ammatory
pathological conditions in the gastrointestinal (GI) state, local activation of the immune system occurs.
tract such as gastroesophageal refl ux disease (GERD), Natural killer cells, monocytes, macrophages, dendritic
infl ammatory bowel diseases (IBDs), chronic pancreatitis, cells, mast cells and granulocytes usually elicit the fi rst
and cholangitis-related cholangiocarcinoma illustrate this immune response and initiate infl ammation. Of the many
link. As a barrier to the environment and as the main cell types active during chronic infl ammatory response,
[1]
organ system for digestion and absorption of food, the
GI tract is exposed to many substances and stimulants. This is an open access article distributed under the terms of the Creative
Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows
others to remix, tweak, and build upon the work non-commercially, as long as
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How to cite this article: Ida S, Watanabe M, Baba H. Chronic
infl ammation and gastrointestinal cancer. J Cancer Metastasis Treat
DOI: 2015;1:138-43.
10.4103/2394-4722.166994
Received: 27-07-2015; Accepted: 11-08-2015.

138 © 2015 Journal of Cancer Metastasis and Treatment ¦ Published by Wolters Kluwer - Medknow