Potential for common bacteria to cause colorectal cancer

Student guest post by Desiré Christensen

Colorectal cancer (aka colon cancer) includes cancers of the colon, rectum, and appendix. Colorectal cancer is more common in developed countries (e.g. United States and Japan) compared to developing countries in Africa and Asia. Each year in the United States, there are around 150,000 cases of colorectal cancer diagnosed and about 50,000 people die from this cancer. Risk factors for colorectal cancer include lifestyle factors (e.g. habitual alcohol use; high-fat, low-fiber diet; obesity; sedentary lifestyle; smoking), family history of intestinal polyps or colorectal cancer, and medical conditions (e.g. diabetes, familial polyposis syndromes, hereditary non-polyposis colon cancer syndrome, inflammatory bowel disease, intestinal polyps). [1]

Lifestyle factors are considered important risk factors for colorectal cancer, and they are modifiable unlike family history. Among the most important determinants of colorectal cancer are dietary habits. High-fat, low-fiber diets are associated with an increased risk for colorectal cancer. Diets with a protective effect include those high in vegetables, fruits, fiber, folate, and calcium. [2]

In addition to the risk factors listed above, an infectious cause of colorectal cancer has been suggested. Many bacterial species inhabit the human colon. Some may be friends, and others foes. Friendly colonic bacteria help with digestion, and in return, the colon provides the bacteria a place to live. The presence of friendly bacteria generally goes unnoticed by the host. Other bacteria in the colon may be harmful and are being investigated as potential causes for irritable bowel disease [3] and colorectal cancer. Enteroccocus faecalis (or E. faecalis) is one such bacterium under study for its role in colorectal cancer.

E. faecalis is common and present in most colons. It lives in disease-free individuals as well as people with colorectal cancer. For most, E. faecalis appears to be harmless. But recent studies have shown evidence that E. faecalis is not an innocent bystander in susceptible hosts.[4] The question arises: How could E. faecalis cause cancer in some and be harmless in others?

A characteristic feature of colorectal cancer is genomic instability. Genomic instability refers to chromosomal rearrangement, duplications, and other types of DNA damage. Theories have developed to explain how E. faecalis could contribute to genomic instability. One theory is that E. faecalis produces free radicals such as extracellular superoxide and hydrogen peroxide. Free radicals are highly reactive with other molecules. The free radicals could directly cause mutations in colonic DNA; it is also possible for free radicals to form carcinogens indirectly from dietary procarcinogens (a substance that becomes a carcinogen after being altered). [4]

Results from a study by Huycke et al [3] supports this theory. The investigators found that E. faecalis produces extracellular superoxide and reactive oxygen species capable of causing genomic instability. Free radical production by E. faecalis has the potential to damage DNA in the colon. If production of these free radicals becomes chronic, DNA damage would be ongoing leading to increased genomic instability and mutations. [4]

Dietary risk factors could be combined with the theory about DNA damage induced by E. faecalis to explain some cases of colorectal cancer. An interaction between diet and E. faecalis could also explain why some people develop cancer and others remain disease free. High-risk diets include diets rich in meat and iron. High concentrations of iron in the colon could accelerate formation of free radicals and mutagenic products. Low-risk diets such as those rich in fruits, vegetables and fiber, contain antioxidants that can "round-up" free radicals and reactive oxygen species to limit the potential for DNA damage. Dietary intake could influence the amount and types of carcinogens E. faecalis and other bacteria produce in the colon. Studies are needed to investigate the interaction between infectious causes such as E. faecalis and dietary intake. [5]

The link between colorectal cancer and an infectious agent has been investigated for other bacteria. Streptococcus bovis (S. bovis) has also been linked to colorectal cancer. A case-control study was done to determine the presence of S. bovis in 16 patients with colonic cancer and 16 age matched controls. The presence of E. faecalis was determined by looking for antibodies against E. faecalis. More antibodies often indicate a larger response by the host to bacteria in the body. An increase in antibodies against S. bovis was detected in patients with colonic cancer, but an increase in antibodies against E. faecalis was also seen. In fact, there was a greater increase in antibodies against E. faecalis compared to S. bovis. [5]

There are few epidemiological studies on E. faecalis in colorectal cancer. One study collected stools from patients undergoing colonoscopy who had no prior history of colonoscopy or colorectal cancer. Enterococci were later isolated from the stool samples. Free radical producing enterococci were found in 40 percent of the stool samples. No association was found between colonization with enterococci and colorectal cancer. The study had limitations. The patients were not tracked long enough to study chronic infection and genomic instability that occurs over decades instead of years. In addition, the presence of any enterococci was evaluated instead of focusing on E. faecalis. It is possible that E. faecalis differs significantly from other enterococci in the ability to cause colorectal cancer. [6]

Much remains unknown about the cause of colorectal cancer. Research linking lifestyle factors and infectious causes is lacking. There is a need for more epidemiological studies and studies describing potential pathways leading to the development of cancer. E. faecalis, or any other infectious cause, has not yet been definitively associated with colorectal cancer. Lifestyle factors and family history will remain important risk factors regardless of an infectious cause, but these factors may interact with bacteria found in the colon and help explain why some individuals are at an increased risk for colorectal cancer.

References
1.Colorectal Cancer Overview. (1999) Colon Cancer (Colorectal Cancer). Retrieved 4/10/2010, from Healthcommunities.com.

2.Sandler RS. (1996) Epidemiology and risk factors for colorectal cancer. Gastroenterol Clin North Am; 25(4):717-735.

3.Balish E and Warner T. (2002) Enterococcus faecalis induces inflammatory bowel disease in interleukin-10 knockout mice. Am J of Path; 160:2253-2257.

4.Huycke MM, Abrams V, and Moore DR. (2002) Enterococcus faecalis produces extracellular superoxide and hydrogen peroxide that damages colonic epithelial cell DNA. Carcinogenesis; 23(3):529-536.

5.Darjee R and Gibb AP. (1993) Serological investigation into the association between Streptococcus bovis and colonic cancer. J Clin Pathol; 46:1116-1119.

6.Winters MD, Schlinke TL, Joyce WA, Glore SR, Huycke MM. (1998) Prospective case-control study of intestinal colonization with enterococci that produce extracellular superoxide and the risk for colorectal adenomas or cancer. Am J Gastroenterol; 93(12):2491-2500.