There is mounting evidence that interactions between our genes and environment can give rise to cancer. Plus, more recently, it has become clear that the environment is not just around us, but also within us, in the form of the trillions of microbes that inhabit our bodies and outnumber our own cells.
Now, a new study of rats supports a growing body of evidence that the microbes in our gut do more than help us digest food, they may also affect our susceptibility to colon cancer.
Increasingly, researchers are discovering that cancer is linked to changes in the gut microbes living in our intestines - what is known as the gut microbiota, and commonly referred to as gut bacteria.
For instance, a study published recently suggests gut bacteria may have a role in bile duct cancer.
In the new study, the researchers used rats to explore the relationship between colon cancer and gut microbiota.
They implanted embryos of a genetic strain of rats prone to develop colon cancer into the uterus of three different strains of surrogate mothers.
Each strain of surrogate rat mothers had different compositions of gut microbiota, which the researchers refer to as F344/NHsd (F344), LEW/SsNHsd (LEW), and Crl:SD (SD).
The strain of cancer-prone pups the team used typically develop colonic tumors at age 2-4 months. In this case, the team found that at 1.5 months, the composition of the young rats' gut microbiota was similar to that of their surrogate mothers.
The researchers examined the young rats for tumors at age 6 months. They found rats with LEW gut microbiota developed significantly fewer tumors than rats with F344 or SD gut microbiota.
In fact, the researchers found two of the rats with LEW gut microbiota did not have any colon tumors at all.
The team also observed that rats with F344 gut microbiota had more tumors if they had higher levels of Peptococcaceae and Akkermansia muciniphila bacteria in their gut.
Differences in loss of heterozygosity
Another interesting finding is that the tumors in the rat pups differed in a genetic feature that occurs often in cancer called loss of heterozygosity (LOH). The extent of LOH difference among the tumors depended on which gut microbiota type the pup had.
Heterozygosity is where an organism carries different versions of the same gene. In the case of rats, as in humans, this would normally be two: one from each biological parent.
Having two different versions of the same gene allows for the fact that one could be a cancer-causing mutation inherited from one parent, and the other could be a normal version, and that the normal version will dominate.
However, an increase in LOH means that more cells only have one version of the gene; if this involves loss of the normal version, then it creates cells that are more likely to show malignant growth if the altered gene is, for example, a tumor suppressor gene.
In this study, the researchers tested for LOH in a tumor suppressor gene and found it differed according to which type of gut microbiota environment the tumor arose in.
The wall of the colon comprises several layers. Colon cancer starts in the mucosa - the innermost layer that surrounds the open space within the tube.
Excluding skin cancers, colorectal cancer - where cancer starts in the colon or rectum - is the third most commonly diagnosed cancer in the United States.
The American Cancer Society estimate that in the U.S. in 2016, there will be 95,270 new cases of colon cancer and 39,220 new cases of rectal cancer.
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