**Inflammation, Immune System and Cancer**

388 Advances in Cancer Therapy

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**18** 

 *Ireland* 

**The Role of Inflammation in Cancer** 

Cancer is a pro-inflammatory disease. The link between inflammation and cancer was first noticed over 150 years ago. In 1863, Virchow observed that tumours tend to occur at sites of

Epidemiological studies have recently emerged which support the association between cancer and inflammation. Viruses and bacteria cause chronic inflammation and are significant risk factors in the development of malignancy. Human papilloma viruses, hepatitis B, hepatitis C and helicobacter pylori are well studied examples of this phenomenon which result in cervical cancer, hepatocellular cancer, lympho-proliferative disorders and gastric cancer respectively. Furthermore, increased risk of malignancy is associated with chronic inflammation caused by chemical and physical agents (Gulumian, 1999). In addition to epidemiological data, gene-cluster polymorphisms that lead to increased levels of pro-inflammatory cytokine release are associated with a poorer prognosis and disease severity in cancer patients (Warzocha, 1998; El-Omar, 2000). Moreover, the fact that chronic use of NSAIDs, such as aspirin are shown to reduce the incidence of numerous cancer types including colon, lung and stomach, gives additional supporting evidence for

Recent studies have implicated an inflammation-induced protein called nuclear factor kappa B (NF-κB) as a central figure in the link between cancer and inflammation. In 1986, Baltimore et al., originally discovered NF- κB as a factor in the nucleus of B cells that binds to the enhancer of the kappa light chain of immunoglobulin (Sen, 1986). NF- κB activity is considered a hallmark of inflammation. It is shown that NF-κB manipulation can convert inflammation-driven tumour growth into inflammation-induced tumour regression (Luo, 2004). Furthermore, many oncogenes and carcinogens can cause activation of NF-κB, whereas chemicals with chemo-protective properties can interfere with NF-κB activation

In unstimulated cells, the majority of NF-κB complexes are kept predominantly cytoplasmic and in an inactive form by binding a family of inhibitors known as Inhibitor-κB (IκB). The NF-κB pathway can be activated by numerous stimuli including bacteria, viruses and proinflammatory cytokines especially tumour necrosis factor (TNF). Phosphorylation of NF-κB bound I-kappa-B kinases (IκK) on two conserved serine residues within the N-terminal

**1. Introduction** 

chronic inflammation (Balkwill, 2001).

**2. NF-κB – A key player** 

(Bharti, 2002).

the link between inflammation and cancer (Wang, 2003).

O'Leary D.P., Neary P.M. and Redmond H.P. *Department of Academic Surgery, Cork University Hospital* 
