Chronic infection and inflammation contribute to as many as 25 percent of cancers worldwide, according to researchers, and City of Hope cancer biologists may have found why.
A City of Hope team led by Gerd Pfeifer, Ph.D., Lester M. and Irene C. Finkelstein Chair in Biology and chair of the Department of Cancer Biology, found a telltale clue in special mice that had inflammatory bowel disease linked to intestinal cancer. These mice had a key change to their DNA structure, the team reported in a recent issue of Cancer Research.
This change, called methylation, amounts to a chemical “cap” in certain places in the genetic code. Cells add or remove methylation caps to turn genes on or off as needed. When methylation gets out of hand, the cells lose control, which can lead to cancer.
|Maria Hahn, foreground, and Torsten Hahn examine data that suggest inflammation alters DNA to cause cancer. (Photo by Darrin S. Joy)|
To learn more about inflammation’s effect on methylation, the biologists studied mice that were developed by Division of Radiation Biology researchers Fong-Fong Chu, Ph.D., associate professor, and Steven Esworthy, Ph.D., assistant research scientist. Chu and Esworthy genetically engineered the mice to have inflammatory bowel disease that often leads to intestinal cancer.
The team discovered the engineered mice had abnormal patterns of methylation caps in their genes. The pattern of methylation strongly matched patterns that show up in tumor cells.
“Inflammation appears to cause abnormal DNA methylation leading to cancer,” said Maria Hahn, Ph.D., postdoctoral fellow in the Division of Biology and lead author on the study.
The researchers also found that 70 percent of the genes with abnormal methylation belonged to a particular group of genes. Previous research suggests that abnormal methylation of genes in this group is directly related to tumor development.
“A link between inflammation and cancer has been apparent for some time,” said Pfeifer. “Now we’re starting to get a picture of the actual mechanism that connects them.”
The team now hopes to gain a better understanding of how inflammation causes the abnormal methylation and why the methylation leads to cancer. The work could help them find genes that, when unmethylated, keep cancer in check.
Other researchers on the study included Torsten Hahn, Ph.D., Dong-Hyun Lee, Ph.D., and Arthur D. Riggs, Ph.D., from the Division of Biology, and Byung-wook Kim, M.S., from the Division of Radiation Biology. The study was funded by the National Institutes of Health and appeared in the Dec. 15, 2008, issue of Cancer Research.