Cancer is a complicated disease. We’re born with a certain number of genetic aberrations that can lead to the disease, and we also pick up some from how we live or what kinds of things we are exposed to. But there’s also another way we acquire DNA changes: simply by having another birthday and living longer. As we age, and our cells continue to divide, they’re more prone to making genetic mistakes when they copy our genome. Some of those mistakes can lead to tumors. But how many cancers fall into the second camp—the ones caused by things we are exposed to in this lifetime?
Researchers from Johns Hopkins caused a furor in 2015 when they determined that well over half—65%—of cancers are actually traceable to random mutations and therefore mostly beyond our control. Now a new study adds to those findings. In a report published in JAMA Oncology, a team led by Mingyang Song, a research fellow at the Massachusetts General Hospital and Harvard T. H. Chan School of Public Health, studied more than 135,000 men and women and determined that lifestyle factors, like diet, smoking and exercise, account for 20% to 40% of cancer risk.
The findings don’t contradict those from the Hopkins group, which focused on how mutations in stem cells as they divide can contribute to cancer risk. In that study, they compared the rates of these mutations across different cells in different parts of the body. Song’s study, on the other hand, analyzed differences in cancer rates among different people in a population.
“In terms of variation of cancer risk across different tissues, I think stem cell division and random mutations do play a role in cancer development,” says Song. “I wouldn’t interpret their results as evidence that we cannot prevent cancer and there is no way to prevent most cancer because it’s random. I wouldn’t interpret their findings that way.”
Instead, taking together the Hopkins finding about how many cancers are random and the new study’s results, we have a fuller picture of what factors contribute to cancer.
They paint a picture of everyone having some baseline level of cancer risk that’s caused by their cells dividing, and the mistakes that those cells make when they copy themselves. On top of that are layered the lifestyle factors that Song identified — things such as smoking, diet and physical activity — that can accelerate or slow down that basal level of mutations that stem cells create.
Another way to look at it, says Bert Vogelstein, professor of oncology at Johns Hopkins, is that while most people focus on the amount of cancer that is preventable — according to most experts, and Song’s paper, anywhere from 20% to 40% — he and his colleague Cristian Tomasetti focused on the remaining 60% to 80% that isn’t. What about people who don’t smoke and eat a healthy diet and get plenty of exercise and avoid the sun? If they get cancer, what’s behind their disease?
“Our study doesn’t address the preventable cases,” says Vogelstein. “What our study tries to explain is all cancers that occur in a low risk group, or at least some fraction of those cancers. Before our paper, people thought it was something we couldn’t explain. We explained it; it’s not some previously undiscovered mutagen that’s present in the environment. It’s something very specific that can be measured precisely—mutations occurring during normal stem cell division.”
Since so many cancers are random but some are not, it makes sense to follow doctors’ orders for prevention.