The second deadliest cancer in the U.S. may be caused not by a poor diet, but by the obesity that follows, suggests a new study of the genetics behind colon cancer.
As obesity rates continue to ascend in the United States, reaching 35.7 percent of the population according to the CDC’s latest figures, the risk for future diseases rises with it. Last June, the American Medical Association reclassified obesity as a disease in itself, rather than a risk factor for other diseases, such as diabetes, heart disease, and high blood pressure. Though scientists have known for a while what risks obesity poses physiologically, the genetic underpinnings are just now starting to emerge.
The recent study comes from the National Institutes of Health. A collaborative team of researchers split ordinary lab mice into two groups; one group carried a human version of the NAG-1 gene — a gene shown in prior studies to protect rodents against colon cancer — while the other group didn’t. Both groups were fed a high-fat diet in which 60 percent of their calories came from lard.
As the research team began to feed the mice, they noticed the no-gene group began to fatten up. The NAG-1 group, curiously enough, stayed trim. They also noticed the NAG-1 group didn’t show the same molecular signals in their gut as the non-gene group. "The obese mice exhibited molecular signals in their gut that led to the progression of cancer, but the NAG-1 mice didn't have those same indicators," co-researcher Dr. Thomas Eling, of the National Institute of Environmental Health Sciences, said in a statement.
Following up on their observation, the team collected samples of the cells from each group’s colons for analysis. Specifically, they looked at a group of proteins called histones. These histones are responsible for packaging and ordering the DNA, along with regulating specific genes. Depending on the chemical reactions taking place in the cell, various tags will bind to the surfaces of the histones and activate genes accordingly.
Dr. Paul Wade, fellow co-researcher from the NIEHS, explained that the obese mice and the NAG-1 mice had wildly different patterns of tagging, a process formally known as acetylation. The patterns in the obese mice resembled those usually found in those with colorectal cancer. And the more weight they carried the greater their activation appeared, implying a link between obesity and colon cancer risk.
In humans, colon cancer typically follows lesions in the colon, which over time eventually turn into precancerous polyps and then full-blown malignant tumors. Despite their lethality, roughly nine out of every 10 people whose cancers are screened and caught early go on to live for at least the next five years. As for their research, Wade and Eling hope to uncover exactly how obesity primes the body to develop colorectal cancer, possibly to develop medications that regulate the genes.
"Once we identify the signaling pathways and understand how the signal is transduced,” explained Wade, “we may be able to design ways to treat colorectal cancer in obese patients.”
Source: Li R, Grimm S, Chrysovergis K, et al. Obesity, Rather Than Diet, Drives Epigenomic Alterations in Colonic Epithelium Resembling Cancer Progression. Cell Metabolism. 2014.