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Colon cancer is associated with bacteria and cell stress

Thu, 09/20/2018 - 08:43
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Researchers at Technical University Munich have reported colon cancer is caused by bacteria and cell stress, more specifically activated transcription factor ATF6 and that chronic inflammation has no effect on cancer development in the colon. It was known that ATF6 regulates stress in cells, and the intensity and duration of activation is increased with diseases. In this latest study, ATF6 incidence was found to be increased in colon cancer patients.

"We originally wanted to study the role of bacteria in the intestines in the development of intestinal inflammation," explained Professor Dirk Haller from the Department of Nutrition and Immunology at the Weihenstephan Science Centre of the TUM. "However, the surprising result for us was the discovery that bacteria, together with stress in cells, caused tumours (exclusively in the colon) and without the involvement of inflammation."

The investigations, reported in the paper, ‘{{Activated ATF6 Induces Intestinal Dysbiosis and Innate Immune Response to Promote Colorectal Tumorigenesis}}’, published in Gastroenterology, were initially carried out using a mouse model. In germ-free animals in which the activated transcription factor ATF6 regulated stress in the intestinal mucosa (intestinal epithelium), no change could be observed.  As soon as the microbiota were transplanted back into germ-free animals, tumours developed in the colons of the mice. Using Koch's postulates, Haller and his team were able to show that microorganisms are involved in the development of cancer in the colon.

"However, it is not cell stress alone that leads to tumour growth, but the combination of stress and microbiota that favours cancer growth," added Haller, head of ZIEL—the Institute for Food & Health at TUM.

Subsequently, the data of 541 patients with colon cancer were examined. In those cases in which the level of transcription factor ATF6 was significantly increased, triggering stress, the recurrence rate after surgery increased – approximately about 10 percent of patients were at risk of developing colon cancer a second time.

"In certain patients, the protein ATF6 could serve as a diagnostic marker for an increased risk of colon cancer and could indicate the start of therapy at an early stage," concluded Haller. “Microbial therapy is conceivable, when we know more about the composition of the bacterial flora. What has become clear, however, is chronic inflammation has no effect on cancer development in the colon."

To access this paper, please click here