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In the U.S., colorectal cancer is the third most common form of cancer, and the second most deadly form of cancer (CDC, Colorectal Statistics). Risk factors for colorectal cancer include pre-existing inflammatory bowel disease, colitis, or Crohn’s disease; hereditary factors; sedentary lifestyle, low-fiber diet, obesity, and use of alcohol or tobacco. Over 90% of colorectal cancer diagnoses occur in people over age fifty (CDC, Colorectal Risk Factors).
A recent review found that only about 20% of colorectal cases can be attributed to heritable origins; thus, in the vast majority of cases the causes are likely to include significant environmental factors, such as diet, exposure to mutagens, or infection (Terzić et al 2101).
There is a long-established association between cancer and the immune system’s inflammatory response (Coussens and Werb 860). Inflammation has been implicated in tumor growth and metastasis, and there is evidence that inflammation may also play a key role in the mutagenesis that initiates tumor growth, especially in colorectal cancer that is preceded by colitis or irritable bowel disease (Terzić et al 2104).
Increased understanding of the role of nonhuman microbial cells in carcinogenesis is a more recent development. For instance, it is now understood that cervical cancer is caused in large part by prior infection by any of several oncogenic human papillomaviruses viruses (National Cancer Institute, HPV and Cancer). It has recently become understood that the inflammation in stomach ulcers caused by the bacterium Helicobacter pylori can also cause mutagenesis that leads to stomach cancer (Akst; National Cancer Institute, H. pylori and cancer).
A study published in March, 2014 explores the relation of intestinal bacteria to colorectal cancer in a mouse model of the disease. The HBUS mouse has been developed to express a gene for heparin-binding EGF-like growth factor throughout the intestine. This modification causes the HBUS mouse to develop polyps in the cecum of the colon. To test the role of bacterial gut flora in the initiation of these tumors, the HBUS mice were treated with antibiotics that reduced the intestinal bacteria. This caused a dramatic reduction in cecum polyps, as compared with a control group that received no antibiotics (Bongers et al 457).
The Bongers et al study suggests that bacteria in the colon play an essential role, not only in tumor growth and metastasis, but also in the initiation of tumors in colorectal cancer. The mechanism, as hypothesized by Jobin (385) is this: The colon is lined with simple columnar epithelial cells that are rich in goblet cells. These goblet cells secrete the mucins that mix with water to create the protective mucus that coats the inner lining of the colon. (When healthy, this mucus prevents pathogenic microorganisms from entering the epithelial inner lining of the colon Martini & Nath 121-122). Jobin (385) believes it may be Akkermansia muciniphila that breaks down the mucin, allowing various species of the Clostridium family to enter the epithelial cells and cause inflammation. Once the inflammatory response occurs, various species of reactive oxygen are able to enter the inflamed cells, leading to DNA damage and possible mutation (Federico et al 2381-2384; Coussens and Werb 864; Terzić et al 2104-2105).
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One might be tempted to suppose that anyone at increased risk of colorectal cancer should receive prophylactic antibiotic treatment to prevent damage to the mucosal layer of the colon and subsequent inflammation of the epithelial cells lining the colon. The problem with that approach is that the relation of human physiology to our human microbiota – the many microorganisms that live on and in us – is very complex. We have evolved together with these organisms over millennia (Akst; Terzić et al 2106-2107). Through this co-evolution, we have become interdependent with these organisms to the point that their elimination can cause a different set of health problems. For that reason, it is not usually helpful to kill off all the bacteria in the colon, or even entire categories of bacteria, such as the gram-negative, gram-positive, or other groups of bacteria that could be targeted. Instead, approaches to the prevention and treatment of colorectal cancer must be very much more specific.
Akst, Jef. “Human-Pathogen Coevolution: Helicobacter pyloristrains that share ancestry with their human hosts are less likely to cause severe disease.” The Scientist 13 January 2014: (no page). Web. 29 April 2014.
Bongers, G. et al., “Interplay of host microbiota, genetic perturbations, and inflammation promotes local development of intestinal neoplasms in mice,”The Journal of Experimental Medicine, 211.3 (2014): 457-472.
Centers for Disease Control and Prevention. What are the Risk Factors, 2013. Web. 29 April 2014. <http://www.cdc.gov/cancer/colorectal/basic_info/risk_factors.htm>
Centers for Disease Control and Prevention. Colorectal Cancer Statistics, 2014. Web. 29 April 2014. <http://www.cdc.gov/cancer/colorectal/statistics/>
Coussens, Lisa M. and Zena Werb. “Inflammation and cancer.”Nature,420.6917 (2002): 860–867.
Federico, A., Morgillo, F., Tuccillo, C., Ciardiello, F. and Loguercio, C., “Chronic inflammation and oxidative stress in human carcinogenesis.” Int. J. Cancer, 121. (2007): 2381–2386.
Jobin, Christian. “Do bugs define cancer geography” The Journal of Experimental Medicine, 211.3 (2014): 385.
Martini, Frederic H. and Judi L. Nath. Fundamentals of Anatomy & Physiology. 8th Ed. San Francisco: Pearson, 2009.
National Cancer Institute, National Institutes of Health. HPV and Cancer, 2012. Web. 29 April 2014. <http://www.cancer.gov/cancertopics/factsheet/Risk/HPV>
National Cancer Institute, National Institutes of Health. Helicobacter pylori and Cancer, 2013. Web. 29 April 2014. <http://www.cancer.gov/cancertopics/factsheet/Risk/h-pylori-cancer>
Terzić, Janoš, Grivennikov S, Karin E, Karin M. “Inflammation and Colon Cancer.” Gastroenterology, 138.6 (2010): 2101-2114.