Dear list, I thougt you all might find this of interest. It's from HMS BEAGLE, a very good science site that has a news letter you may subscribe. I read one cancer reseacher to equate research moneys direction being like losing a dime on one side of the street but lookng for it on the other side because that's where the street light is! <<<<<<<<<<<<<<<<<<>>>>>>>>>>>>>>>>
Is Bacterial Infection Carcinogenic? by Kirstie Saltsman Posted February 2, 2001 · Issue 95 Abstract Can bacteria cause cancer? The author discusses the discovery of a link between bacterial infection and cancer, the mechanisms by which bacteria cause cancer, and the potential for treatment. Although his work was later called into question, Johannes Fibiger, the winner of the 1926 Nobel Prize in physiology, may not have been too far off the mark. He was awarded the prize for his discovery that a parasitic worm, Spiroptera carcinoma, causes gastric tumors in rats. While dissecting rats infected with the tuberculosis bacterium, he noticed that some had stomach growths, each of which contained a parasitic worm. The growths later proved to be unrelated to the parasite, and doubt was even cast upon his assertion that the growths were malignant. Nevertheless, the idea that an infectious organism could cause cancer turned out to be accurate and groundbreaking. Infectious organisms cause about 15% of cancers.By the early 1970s, nearly 30 mammalian oncoviruses had been discovered, and it is now estimated that over 15 percent of cancers worldwide are caused by infectious organisms. Although the idea that viruses can cause cancer has been accepted for decades, the idea that bacteria can cause cancer has begun to attract attention only recently. The most established instance of this is the link between Helicobacter pylori infection and gastric cancer, but bacterial infections have also been implicated in other types, such as colon and gall bladder cancers. The mechanisms by which bacteria cause cancer appear to be quite different from those used by viruses. Viruses, by inserting their genomes into host cell chromosomes, can alter expression patterns of host cell genes and disrupt the intricately regulated process of growth control. Human papillomavirus (HPV), for example, which is associated with cervical cancer, induces cellular transformation by inhibiting the host cell tumor suppressors p53 and Rb. In addition, as in the case of human immunodeficiency virus (HIV), viral infection can cause depletion of the immune system, leaving the host less able to destroy cancerous or precancerous cells that arise by spontaneous mutation. Kaposi's sarcoma and non-Hodgkin's lymphoma are now considered AIDS-defining malignancies. Bacterial infections can cause tumors via inflammation.In contrast, bacteria are thought to cause cancer largely via an indirect mechanism. It seems that it is the host's response to infection - inflammation - which damages cells and predisposes them toward becoming cancerous. Phagocytes drawn to the site of infection release reactive oxygen and nitrogen species that can cause DNA mutations and damage cellular proteins and lipids. In addition, loss of cells at the site of infection stimulates cell proliferation in order to regenerate the tissue, a process that leaves the site vulnerable to tumor formation. Proliferating cells are one step closer to uncontrolled cell growth, and are also susceptible to acquiring mutations due to errors in DNA replication. Although inflammation and its molecular consequences are now known to be major risk factors in developing gastric adenocarcinoma in those infected with H. pylori, it was not until fairly recently that a connection was made between the two. Although the association between H. pylori and gastric cancer is among the better known examples of a bacterial cause for cancer, Julie Parsonnet, associate professor of medicine at the Stanford University School of Medicine's proposed ERID (Emerging and Re-emerging Infectious Diseases) program, points out that it is not the first such association to be made. She says that "people have long recognized that chronic skin and bone infections with bacteria can lead to aggressive skin cancers." Although it had been suspected for some time that a widespread environmental determinant was an etiologic factor in the development of gastric cancer, it was not until 1991 that H. pylori, a gram-negative, rod-shaped bacterium, was found to be involved. Over 50 percent of the world's population is infected with H. pylori; however, in most cases, infection has no serious clinical consequences. A complex interplay between host and bacterial factors seems to determine the outcome of infection. Among the bacterial factors is a group of genes - whose functions are largely unknown - localized in a cassette called the cag pathogenicity island. cag+ strains are more virulent than their cag- counterparts, and there is a strong correlation between infection with cag+ strains and the occurrence of both gastric cancer and duodenal ulcer disease. However, those with H. pylori-induced ulcers are less likely than the general population to contract gastric cancer, a finding that underscores the importance of host factors in disease outcome. Host genes influence susceptibility to bacterial tumorigenesis.Because host factors are thought to influence susceptibility to disease, a number of research teams are currently trying to pinpoint disease-predisposing genetic determinants within the host. Among those that are already known to influence the risk of gastric cancer is the gene for interleukin-1-beta (IL-1-beta). Elevated levels of this cytokine promote inflammation and suppress gastric acid secretion, which allows for more extensive bacterial colonization of the stomach. In an attempt to identify other host genes that influence the risk of gastric cancer, Karen Guillemin, a postdoctoral research fellow in Stanley Falkow's lab at Stanford University, has devised a strategy based on the use of human DNA microarrays and a tissue culture model of infection. By comparing the host genes induced by the more virulent cagA+ strain with those induced by a cagA- strain, she has distinguished a subset that may be involved in disease. Some of these genes appear to be involved in cell signaling or in remodeling the cell ultrastructure, both of which may set a cell on a course toward malignancy. However, others are likely to promote cancer indirectly by promoting the growth of virulent strains. "Because infection with H. pylori is a long-term, often lifetime condition, and because H. pylori populations are known to undergo a lot of genetic changes and diversification, similar to viruses, a complexity that I think will emerge is that certain host genes will be found to promote particular gastric environmental conditions that select for more or less virulent bacteria," says Guillemin. Because only 1 percent of infected individuals have the misfortune of contracting the disease, genetic determinants within both host and bacteria are likely to affect the outcome of infection. Vaccination against H. pylori may fight cancer well.The finding that bacterial infections can cause cancer is exciting because unlike a genetic predisposition or an environmental factor, infections often can be treated or prevented. A recent study published in the Journal of the National Cancer Institute has shown regression of precancerous lesions upon treatment with antibiotics among a high-risk population in southwestern Columbia. Other studies are currently underway. However, the use of antibiotics is unlikely to take hold as a widespread preventive measure. The cost would preclude such a strategy, as would the risk of inducing the emergence of antibiotic-resistant strains. A more practical approach would be to induce protection by vaccination, and trials in mouse models of infection have already yielded promising results. Oral and intranasal vaccination has provided mucosal immunity, and systemic vaccination has also been shown to provide protection in the mouse model. It remains to be seen if these promising results will be reflected in the human trials currently being undertaken. In 1966, Peyton Rous was awarded the Nobel Prize in medicine for his discovery that a virus (the Rous sarcoma virus) could cause cancer. Now, a mere 35 years later, a significant proportion of liver cancer is preventable thanks to a vaccine against hepatitis B. In addition, vaccines against human papillomavirus are now being tested in an effort to combat cervical cancer, and Epstein-Barr-virus-related tumors in HIV patients are becoming less common thanks to immunotherapy. Just as the discovery of the viral origin of certain cancers led to useful therapies, it is probably not overly optimistic to expect that the discovery of a link between bacterial infection and cancer will soon lead to effective treatments and eventually curtail the number of lives lost to this deadly disease. Kirstie Saltsman is a freelance biomedical writer based in Baltimore. 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