Sunday, August 5, 2012

Inflammation and Cancer

Cancer is associated with inflammation and elevated levels of inflammatory markers.  Inflammation increases genetic instability, DNA damage and cell proliferation and promotes tumour development and growth [1] [2]. 

Pro-inflammatory cytokines (such as IL-1, IL-6, TNF-α) are elevated in tumour cells from the earliest stages of development.  They can increase tumour progression and PTP1B, promote angiogenesis, growth and proliferation of tumour cells and inhibit apoptosis of tumour cells.  Tumour cells produce and secrete IL-1 and TNF-α for these reasons [1] [2] [3] [4] [5]. 

NFκB can be induced by pro-inflammatory cytokines (IL-1, TNF-α), inflammatory substances (LPS, ROS, ionising radiation) and hypoxia.  NFκB activates gene expression for pro-inflammatory cytokines, enzymes for pro-inflammatory eicosanoids (such as COX2), adhesion molecules, angiogenesis, inhibiting apoptosis.  NFκB promotes the proliferation and survival of malignant cells and metastasis and inhibits the adaptive immune system [1] [2] [4] 

People with chronic inflammatory diseases are more like to have cancer in the inflammed tissues:

  • People with IBD are 5-7 times more likely to develop colorectal cancer [1]
  • 43% of people with ulcerative colitis develop colorectal cancer after 25-35 years [1]
  • Papillary thyroid cancer is associated with Hashimoto’s thyroiditis and Grave’s disease (two autoimmune thyroid diseases) [5]
  • H. pylori infection is associated with gastric cancer and gastric mucosal lymphoma [2], in particular the degree of inflammation from H. pylori infection is associated with gastric cancer [6]
  • Prostatitis is associated with prostate cancer [2]

Further evidence to support the role of inflammation in cancer: 

  • In an animal model of IBD (from IL-10 deficiency) there were 4-5 times more DNA mutations [2]
  • The development of hepatocellular carcinoma in mice carrying HBV genes is associated with inflammation and liver damage [7]
  • Increasing inflammatory cells or pro-inflammatory cytokines promotes the development of tumour cells [2]
  • Levels of DNA oxidation (8-oxo-dG) are increased in those with chronic inflammatory diseases and chronic infections [8]
  • People with IL-1 producing tumours tend to have poorer outcomes [1]
  • In an animal model of IBD colorectal cancer can be inhibited by blocking TNF-α [1]
  • Blocking inflammatory signals (such as IL-1, TNF-α, NFκB and STAT3) decreases the incidence and spread of cancer [1]
  • Anti-inflammatory drugs such as NSAIDs are associated with a reduced risk of developing some cancers, relapse, new tumours and mortality relating to these cancers [1] [2]

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