Helicobacter pylori and cancer

Helicobacter pylori (H.pylori) is not a virus at all but a bacterium, in fact one of very few bacteria that are able to survive and grow in the stomach. About half the world's population are infected with H-pylori, the highest rates of infection being in poorer countries where and it is mainly contracted in childhood 1.

Chronic infection causes an inflammation of the stomach that in many people goes unnoticed but in others leads to gastric or duodenal ulcers. A long-term consequence of chronic infection is that H. pylori-infected people have a 4- to 6-fold increased risk of subsequently developing gastric adenocarcinoma, the most common form of stomach cancer worldwide 2, 3, 4.

The fall in rates of gastric cancer in many countries has been linked to decreasing prevalence of H. pylori infection.9 A study published in December 2011 estimated that around a third of stomach cancers in the UK in 2010 were linked to infection with H. pylori.10 Infected people are also at risk of developing a rare B cell tumour, so called MALT lymphoma 5. Both types of cancer provide examples of how a bacterium, an agent that (unlike a virus) does not grow inside target cells, can nevertheless predispose such cells to becoming malignant by indirect means.

Figure 7.1: Stomach cancer age-standardised incidence per 100,000 population

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Gastric carcinoma

How H. pylori predisposes gastric epithelial cells to become cancerous is not fully understood 6. However one clue is that only certain strains of H. pylori, with a set of additional genes involved in protein secretion, are particularly linked to gastric carcinoma. Such strains are able to inject one of these additional protein products, CagA, into epithelial cells, and the cellular changes induced by this protein appear important to the onocogenic process. 

Equally important is the fact that H. pylori infection induces inflammation of the stomach, leading to the release of a variety of chemical messengers ('cytokines') from the incoming inflammatory cells. People who carry 'high producer' versions of particular cytokine genes are found to be at special risk of cancer development, so clearly over-production of these natural chemicals affects the local environment and increases the chances of cancerous change. Cancer development is a slow process and by the time gastric carcinoma appears, the H. pylori infection itself has often subsided. By then the initiating role played by H. pylori in the cancer process is already complete.

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Gastric "MALT" lymphoma

The link between H. pylori infection and MALT lymphoma illustrates how subtle indirect mechanisms of tumour causation can be 7, 8. Part of the chronic inflammatory response to H. pylori described above involves T cells that specifically recognise the bacterial infection and try to remove it by secreting particular cytokines. In response to these signals, B cells are attracted into the area and start to grow and divide. The chronic stimulation of these B cells by H. pylori-specific T cells increases the chances of them acquiring accidental chromosomal translocations.

Specific chromosomal changes are seen in MALT lymphomas and their analysis has led to the identification of hitherto undiscovered oncogenes. Although oncogene activation is clearly important in the development of MALT lymphomas, tumour growth often remains dependent on the cytokines produced by T cells reacting to the H. pylori infection. So the bacterium is still there when the lymphoma arises, and its removal by antibiotic treatment leads in the majority of cases to a complete cessation of lymphoma growth.

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References for Helicobacter pylori and cancer

  1.  Parkin, D.M., The global health burden of infection-associated cancers in the year 2002. Int J Cancer, 2006. p.3030-44
  2.  IARC, Schistosomes, liver flukes and Helicobacter pylori. IARC Monograph 61, in, Editor^Editors. 1994: Lyon.
  3.  Marshall, B., Helicobacter pylori: 20 years on. Clin Med, 2002. 2(2): p.147-52.
  4.  Pinto Santini, D. and N.R. Salama, The biology of Helicobacter pylori infection, a major risk factor for gastric adenocarcinoma. Biomarkers Prev, 2005. 14(8): p. 1853-1858.
  5.  Parsonnet, J. and P.G. Isaacson, Bacterial Infection and MALT lymphoma. N Engl J Med, 2004. 350: p. 213-215.
  6.  Stoicov, C., R. Saffari, and X.e.a. Cai, Molecular biology of gastric cancer: Helicobacter infection and gastric adenocarcinoma: bacterial and host factors responsible for altered growth. Gene, 2004. 341: p. 1-17.
  7.  Isaacson, P.G. and M.Q. Du, MALT lymphoma: from morphology to molecules. Nature Rev Cancer, 2004. 4: p. 644-653.
  8.  Isaacson, P.G. and M.Q. Du, Gastrointestinal lymphoma: where morphology meets molecular biology. J Pathol, 2005. 205: p. 255-274.
  9.  Vyse, A.J., et al., The burden of Helicobacter pylori infection in England and Wales. Epidemiol Infect, 2002.128(3):411-7.
  10.  Parkin, DM (2011) Cancers attributable to infection in the UK in 2010. Br J Cancer 105 (S2):S49-S56; doi: 10.1038/bjc.2011.484