It is not only genetics that predispose to bowel cancer. According to new research in mice published in the March 3, 2014 issue of JEM/The Journal of Experimental Medicine, microbes living in the gut help drive the development of intestinal tumors.
Bowel cancer, also called colon or colorectal cancer, is the third most common non-skin cancer and the second leading cause of cancer-related mortality in men and women in the United States. The available data shows that over the past decade, colorectal cancer incidence and mortality rates have decreased in all racial/ethnic populations except American Indians/Alaska Natives. Men and women have similar incidence and mortality rates through age 50; after age 50, rates are higher in men. While there is a differences between racial and ethnic groups in both incidence and mortality, overall incidence and mortality rates have been declining largely due to increased use of screening tests.
Risk factors for colorectal cancer include increasing age, colorectal polyps, a family history of colorectal cancer, and certain genetic mutations.
Colorectal cancer results from a series of genetic changes (mutations) that cause healthy cells to become progressively cancerous, first forming early tumors called polyps that can eventually become malignant. Although mutations can occur anywhere in the human intestine, certain types of colorectal cancer tend to develop in particular locations, suggesting that additional, non-genetic factors contribute to tumor growth and dictate where polyps appear.
Understanding the interplay between genetic mutations, gut microbes, and inflammation may lead to novel diagnostics and therapies for intestinal cancer…
What is the role of gut microbes
Sergio Lira and his team at the Icahn School of Medicine at Mount Sinai, New York, asked if gut microbes have a hand in tumor development. The researchers had noticed previously that mice carrying polyp-causing mutations develop polyps only in a limited section of the intestine, despite the mutations being present in all cells along the intestine. In the new study, they treated the mice with antibiotics to disrupt the populations of microbes living in their gut. This treatment prevented the formation of polyps, showing that bacteria are essential for early tumor development in this model. The authors propose that bacteria cross from the gut into the tissue of the intestinal wall, triggering inflammation that promotes tumor growth.
More research needed
While further research is needed to confirm the identity of the cancer-promoting bacteria, the findings suggest it may be possible to reduce the risk of colorectal cancer in genetically susceptible individuals by removing certain types of gut bacteria.
The study results may also help explain some of the nongenetic factors that have been implicated in colorectal cancer. “In addition to genetic changes, various lifestyle-related factors, such as obesity and diet, have been linked to colorectal cancer. Some of these lifestyle factors appear to affect the types of bacteria present in the gut,” Lira explained. “Ultimately, understanding the interplay between genetic mutations, gut microbes, and inflammation may lead to novel diagnostics and therapies for intestinal cancer.”
For more information:
Bongers G, Pacer ME, Geraldino TH, Chen L, He Z, Hashimoto D, Furtado GC, et al. Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice. JEM/The Journal of Experimental Medicine, March 3, 2014 doi: 10.1084/jem.20131587. [Article]
Photo: The development of intestinal tumors (polyps) in mice (left) was prevented by modifying the composition of gut microbes (right). Photo Courtesy: Bongers et al., 2014.
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