Even though the small intestine has a greater cell mass than the colon, it is longer, has a greater surface area and a faster rate of epithelial turnover, the incidence of small bowel cancer is tenfold lower than that of colorectal cancer.
In a recent review article entitled “Host–microbe interactions and spatial variation of cancer in the gut,” published in the journal Nature Review Cancer, authors Fergus Shanahan and Paul W. O’Toole discuss the biological factors behind this apparent discrepancy.
The epithelium of the small bowel and large bowel contrast in the way that damaged DNA is dealt with, since protection through elimination of mutated cells by apoptosis is characteristic of the small intestine, whereas repair and infrequent apoptosis is common in the colon.
This leaves scientists questioning why is the colon so susceptible to cancer?
The majority of colorectal cancers occur through sporadic mutations in genes responsible for regulating the epithelial cell cycle and survival. Moreover, environmental risks such as high-fat diets, sedentary occupations and obesity all account for increased risk.
However, the most immediate environmental factor predisposing to colorectal cancer is the gut microbiota, which is in part defined by these lifestyle variables.
There have been several animal studies that partly explain the complexity of the microbiota in the development of inflammation and cancer.
For example, changes in the microbiota alone are sufficient to cause colitis that can be transferable to healthy hosts. Also, even though pro-inflammatory cytokines like interleukin-17 (IL-17) have the capacity to generate an enhanced cell proliferation response, increasing genotoxic reactive oxygen species, this alone is not sufficient to cause colitis-associated cancer, since carcinogenesis progression is dependent on microbiota composition.
Different types of bacteria have been found to increase the risk of colorectal cancer, such as Streptococcus gallolyticus, Bacteroides fragilis, Escherichia coli and Fusobacterium species. The mechanisms by which these organisms can contribute to carcinogenesis include production of DNA damaging metabolites and their capacity to penetrate colonic mucus, inducing epithelial proliferation and mucosal inflammation.
The clinical potential to inhibit microbial metabolism has been demonstrated through the use of irinotecan, a chemotherapeutic drug used to treat colon cancer.
If researchers can identify new microbial biomarkers of disease risk that could improve on current screening strategies, this would result in a window of opportunity for early prevention of disease.
Colon cancer is significantly related to age, with a median age at diagnosis of 60 years and more. In this group of people, dietary composition has a significant impact on the composition of the microbiota. Thus adjusting the environmental factors that control it makes it possible to reduce the risk of developing colorectal cancer, even at an older age.