A holo'ome approach in colon cancer: we change as we age.

Abstract

More than 90% of colorectal cancer (CRC) cases occur in people 50 years or older. This fact accords with the well‐established notion that many cancers are diseases of old age that result from changes to or the deterioration of our cellular processes. So what specifically goes wrong? “Of cancers that affect both men and women, colorectal cancer is the second leading cancer killer in the United States [and Europe], but it doesn't have to be.” (Centers for Disease Control and Prevention, http://www.cdc.gov/cancer/colorectal/). Genes certainly play a role, but inherited genetic variation only partly explains the predisposition to sporadic CRC. More important, perhaps, are somatic mutations that accumulate in some cells and tumors over the years driving CRC. But such mutations build up at different rates in different people and do not impact all people the same way. Moreover, some somatic mutations are cell division‐driven, accumulating at a presumably constant rate, while others persist because they confer a cell proliferation and survival advantage, or because they provide that advantage in a context‐dependent manner, for example, upon intestinal inflammation. In fact, chronic inflammation establishes an ideal environment in which …