The long view: understanding why cancer strikes late

We all know that cancer happens more often in older people. The reason seems to be that cancer develops slowly, first passing through a series of benign stages. Our understanding of how cancer develops over a lifetime is limited by the extreme difficulty of monitoring these slow changes, but new work reported this week aids this effort by employing mathematical modelling to analyze epidemiological data on the relationship between age and cancer and generating ideas about how cancer progresses over time.

The findings come from Steven Frank at the University of California in Irvine, who analyzed how the rates of breast, prostate, colon, and lung cancers rise with age. Older people do indeed get these cancers much more often, but the increase with age slows down later in life.

In the new work, Frank asks how the passage through the benign early stages of cancer would cause the increase in cancer incidence to slow as one ages. His theory is that, early in life, we are well-protected because all of our cells have many stages to go through before they may become cancerous. As we get older, some of our cells progress through the early stages. By midlife, much of the waiting for the slow passage of the early stages is over. A few of our cells are poised on the brink of cancer, with only a few steps to go.

So, early in life there are many steps to pass and cancer incidence less frequent. When people are older, cancer strikes frequently because only one or two short steps remain. Cancer incidence is high, but does not increase so much as one gets even older, because those last steps could strike at any time. Frank develops a general model for how cancer progresses then uses it to explain the observed differences between tissues (e.g., prostate vs. breast) in age-specific cancer acceleration.

New genetic techniques will soon allow scientists to look at the genetic changes in cells that cause cancer. If Frank is right, then everyone will have cells stepping along through the early stages of cancer progression as they get older. The actual incidence of cancer at different ages in different people can then be linked to the slow changes that happen over the course of our lives.