Unavoidable typos in DNA help fuel cancer

WASHINGTON -- Cancer patients often wonder "why me?" Does their tumor run in the family? Did they try hard enough to avoid risks such as smoking, too much sun or a bad diet?

Lifestyle and heredity get the most blame, but new research suggests random chance plays a bigger role than people realize: Healthy cells naturally make mistakes when they multiply, unavoidable typos in DNA that can leave new cells carrying cancer-prone genetic mutations.

How big? About two-thirds of the mutations that occur in various forms of cancer are due to those random copying errors, researchers at Johns Hopkins University reported Thursday in the journal Science.

That doesn't mean most cases of cancer are due solely to "bad luck." It takes multiple mutations to turn cells into tumors -- and a lot of cancer is preventable, the Hopkins team stressed, if people take proven protective steps.

Thursday's report is an estimate, based on a math model, that is sure to be debated hotly by scientists who contend those unavoidable mistakes of nature play a much smaller role.

But whatever the ultimate number, the research offers a peek at how cancer may begin.

And it should help with the "why me" question from people who have "done everything we know can be done to prevent cancer, but they still get it," said Hopkins' Dr. Bert Vogelstein, a pioneer in cancer genetics who co-authored the study.

People might inherit some mutations, such as flaws in BRCA genes that are infamous for causing aggressive breast and ovarian cancers in certain families.

More commonly, damage is caused by what scientists call environmental factors -- the assault on DNA from the world around us and how we live our lives. There's a long list of risks: cigarette smoke, UV light from the sun, other forms of radiation, certain hormones or viruses, an unhealthy diet, obesity and lack of exercise.

Then there are those random copy errors in cells -- what Vogelstein calls our baseline rate of genetic mutations that will occur no matter how healthy we live.

One way to think of it: If we all have some mutations lurking in our cells anyway, that's yet another reason to avoid known risks that could push us over the edge.

New cells are formed when an existing cell divides and copies its DNA, one cell turning into two. Every time DNA is copied, about three random mutations occur, Vogelstein said.

We all harbor these kinds of mutations, and most don't hurt us because they're in genes that have nothing to do with cancer or the body's defense mechanisms spot and fix the damage, said Dr. Otis Brawley of the American Cancer Society, who wasn't involved in the new research.

But sometimes the errors hit the wrong spot and damage genes that can spur cancerous growth or genes that help the cell spot and fix problems. Then the damaged cells can survive to copy themselves, allowing important mutations to build up gradually over time. That's one reason the risk of cancer increases with age.