Gut Inflammation can Alter the Epigenome to Boost Cancer

Chronic inflammation can lead to many health problems, and can increase the risk of cancer. Scientists have now learned more about the connection between chronic gut inflammation and colon cancer. This work, which used a mouse model, has shown that cells in the gut can develop a kind of genetic memory of inflammation that can promote the subsequent development of cancer. This genetic memory relies on the epigenome, in which various factors like methyl groups or DNA structure can influence gene expression without altering the genetic sequence. The findings have been reported in Nature.

In this work, the investigators created a mouse model of gut inflammation, and then assessed genetic factors like gene expression and epigenetic patterns. They determined that after inflammation had declined, and tissues seemed to be normal, some cells had an epigenetic memory of the inflammation; certain parts of the genome remained open, even though gene expression was similar to healthy cells.

When the researchers added a genetic mutation that boosts cancer to the gut cells, those with epigenetic changes from inflammation grew bigger tumors. There were groups of cancer-promoting genes that were activated by those epigenetic changes. The investigators concluded that inflammation can lead to epigenetic changes that encourage cancer growth when another mutation happens later.

"This finding is a great example of how our experiences and exposures affect our future health. We've shown that epigenetic changes are the missing piece in how inflammation leads to cancer,” said senior study author Jason Buenrostro, a professor at Harvard University, among other appointments. "We all walk around with cancer-related mutations, but we don't all have cancer. It's not just the genetic mutation that matters—the cell type and the experiences that cell has will determine disease outcomes."

Now the researchers want to know if these epigenetic changes can be found and diagnosed, so that people who are at increased risk of bowel cancers can be identified. The findings will also inform scientists who are looking for treatments for these disorders.

Sources: Broad Institute of MIT and Harvard, Nature