Nearly two-thirds of cancer mutations are attributable to random DNA copying errors that occur naturally as healthy cells divide, according to a new study out Thursday from researchers who years ago controversially proposed that "bad luck" plays a larger role in cancer than environmental factors and inherited genes.
"Most of the time, these (random) mutations don't do any harm. They occur in junk DNA, genes unrelated to cancers, unimportant places with respect to cancer. That's the usual situation, and that's good luck in our paraphrase," Professor Bert Vogelstein of the Johns Hopkins University, whose study was published in the U.S. journal Science, said at a news conference.
"But occasionally they occur in a cancer driver gene, that's bad luck," he said.
Vogelstein's earlier study, published in Science in 2015, created vigorous debate from scientists who argued that their results did not include breast or prostate cancers, and it reflected only cancer incidence in the United States.
This time, the scientists analyzed DNA sequencing and epidemiologic data from nearly 70 countries, representing 4.8 billion people, or more than half of the world's population, looking specifically at mutations that drive abnormal cell growth among 32 cancer types.
The results showed that the high correlations they found in 2015 between cancer incidence and cell divisions are universal rather than confined to the United States.
For example, that 77 percent of mutations in pancreatic cancers are due to random DNA copying errors, 18 percent to environmental factors, such as smoking, and the remaining five percent to heredity.
In other cancer types, such as those of the prostate, brain or bone, more than 95 percent of the mutations are due to random copying errors.
Lung cancer, they noted, presents a different picture: 65 percent of all the mutations are due to environmental factors, mostly smoking, and 35 percent are due to DNA copying errors. Inherited factors are not known to play a role in lung cancers.
Looking across all 32 cancer types studied, the researchers estimated that 66 percent of cancer mutations result from copying errors, 29 percent can be attributed to lifestyle or environmental factors, and the remaining five percent are inherited.
"We hope that this research offers comfort to the literally millions of patients who have developed cancer but who have led near-perfect lifestyles, who haven't smoked, who avoided the sun without sunscreen, who eat perfectly healthy diets, who exercised regularly, (have) done everything we know that can be done to prevent cancer but still get it," Vogelstein said.
"They need to understand that these cancers would have occurred no matter what they did."
In an accompanying article, Martin Nowak of Harvard University and Bartlomiej Waclaw of University of Edinburgh predicted that the new findings by Tomasetti and Vogelstein could once again stimulate a lot of discussion in the medical community.
"The findings point to a clear need for a precise mathematical understanding of cancer," they wrote. "It will take many years to answer in detail the interesting and exciting questions that have been raised."
Professor Lawrence Young, director of Cancer Research Center at the University of Warwick, said while this study is useful in attempting to integrate epidemiological and genome sequencing data, "the message is complex and does not diminish to need to focus on improved approaches to both primary and secondary cancer prevention."
