Is Cancer Risk Mostly Affected By Genes, Lifestyle, Or Just Plain Bad Luck?

Experts say the findings highlight “the importance of secondary prevention, like early detection.” 

While cancer can strike anyone — young or old, unhealthy and healthy — we do have some idea of what can affect risk. Genetics often play a role, for instance, as do lifestyle habits. But according to a new study from Johns Hopkins University researchers, much of cancer risk may actually be due to mere chance.

Cancer develops when stem cells of a given tissue make random mistakes, mutating unchecked after one chemical letter of DNA is incorrectly swapped for another — the equivalent of a cell “oops.” It happens without warning, like the body’s roll of the die. 

For the new study, published in the journal Science, researchers wanted to see how much of overall cancer risk was due to these unpreventable random mutations, independent of other factors like heredity and lifestyle. 

“There is this question that is fundamental in cancer research: How much of cancer is due to environmental factors, and how much is due to inherited factors?” Cristian Tomasetti, PhD, a biomathematician and assistant professor of oncology at the Johns Hopkins University School of Medicine and Bloomberg School of Public Health, tells. “To answer that question, however, the idea came that it would be important to determine first how much of cancer was simply due to ‘replicative chance.’”

To measure this, the researchers plotted the number of stem cell divisions in 31 types of tissues over the course of a lifetime against the lifetime risk of developing cancer in the given tissue. From this chart, the scientists were able to see the correlation between number of divisions and cancer risk — and from that correlation, researchers were able to determine the incidence of cancer in a given tissue due to replicative chance.

Ultimately, researchers found that roughly two-thirds of the cancer incidence was due to this replicative chance, or simply “bad luck.” (However, it’s worth noting researchers did not examine some cancers, such as breast and prostate cancers, because of lack of reliable stem-cell turnover information.)

But don’t assume you’re simply doomed to the hand fate deals you. After additional analysis, researchers found that of the 31 cancers examined, 22 could be explained by “bad luck” — but for the other nine, there was another factor aside from simple chance that likely contributed to the cancer.

This is presumably because environmental and hereditary factors play a role in development. “There are many cancers where primary prevention has huge positive effects, such as vaccines against infectious agents, quitting smoking or other altered lifestyles,” says Tomasetti. 

Incidentally, the cancers where risk could be lowered by primary preventive practices were ones you may expect — diseases like skin cancer, where limiting sun exposure can lower your risk, as well as lung cancer, where avoiding smoking is key. 

Tomasetti says we can still lower our odds of developing cancer in any and all cases, though, especially as preventative research moves forward. Their analysis just indicates that, for many types of cancers, primary prevention like healthy lifestyle habits may not work as well. “This however does not imply at all that there is not much we can do to prevent those cancers,” he says. “It just highlights the importance of secondary prevention, like early detection.”

Since so much of risk is based on random cell division, identifying a mutation before replication goes unchecked throughout the body is, and will continue to be, essential. “It is still fundamental to do what we can in terms of primary prevention to avoid getting cancer, but now we understand better what causes cancer and how relevant the ‘bad luck’ component is, because we have a measure of it,” Tomasetti explains. “This work tells us that randomness plays an important role in cancer, possibly much larger than previously thought. And therefore early detection becomes even more important.”
You can also look at this new research another way, though, according to Tomasetti. “On one side, it actually strengthens the importance at the individual level to avoid risky lifestyles,” he explains. “If my parents smoked all their lives and did not get lung cancer, it is probably not because of good genes in the family, but simply because they were very lucky. 

“I would be playing a very dangerous game by smoking,” Tomasetti says. See? Healthy habits do count.