Inflammation-related carcinogenesis: current findings in epidemiological trends, causes and mechanisms

Abstract

Inflammation is a definite cancer-causing factor as revealed by cumulative basic, clinical and epidemiological studies. It is mostly induced by infectious agents. For instance, infection with papillomaviruses associates with anogenital cancers, especially cervical cancers; Helicobacter pylori infection of the stomach tends to increase the risk of stomach cancer; chronic hepatitis B & C viruses and fluke infections of the liver increase liver cancers; autoimmune diseases, e.g., inflammatory bowel diseases, associate with development of colorectal cancer, and aerial irritants (foreign bodies) such as asbestos or fine particulate matter (PM2.5) in outdoor air increase malignant pleural mesotheliomas or lung cancers. These are typical examples of inflammation-related carcinogenesis. It is apparent that the pathogens to induce inflammatory reactions in specific organs are not related to each other. However, the underlying pathogenesis in common is to induce and/or sustain inflammation. In this article, I would like to review the up-to-date findings of epidemiological trends, causes and mechanisms of inflammation-related carcinogenesis.

Keywords: carcinogenesis; inflammation; mouse model.

Fig. 1.

Causes of cancer differ from country to country. Europe, excluding east Europe; Africa, representing sub-Saharan countries only.

Fig. 2.

A mouse model of inflammation-related carcinogenesis. Regressive cells (QR) spontaneously regress in syngeneic normal mice after subcutaneous injection (A). Tumorigenic conversion was observed in QR cells injected into subcutaneously pre-inserted gelatin sponge (B). Tumorigenic conversion was also observed in QR cells which were mixed with gelatin-sponge-infiltrated inflammatory cells and injected in mice (C). The model was also utilized to screen candidate drugs to prevent inflammation-related carcinogenesis (D).

Fig. 3.

Alteration of key molecules through foreign-body-induced carcinogenesis in mice. A diagram of stepwise molecular alterations in QR cells associated with acquisition of malignant phenotypes, accelerated by inflammation.

Fig. 4.

Advantages of using gelatin sponge for investigating inflammation-related carcinogenesi. There are advantages in using gelatin sponge for analyzing the inflammation-related carcinogenesis since sponge-infiltrated inflammatory cells can be collected by brief collagenase treatment. Then we can quantify inflammation by counting the number of infiltrated cells. Moreover, by using the infiltrated cells, we are able to analyze the inflammation by biological, molecular genetical, and cytological methods.