A new study by scientists at Johns Hopkins provides evidence that random, unpredictable DNA copying «mistakes» account for nearly
The researchers say their conclusions are supported by epidemiologic studies showing that approximately 40 percent of cancers can be prevented by avoiding unhealthy environments and lifestyles. But among the factors driving the new study, they add, is that cancer often strikes people who follow all the rules of healthy
Adds Bert Vogelstein,
Tomasetti and Vogelstein’s research will be published Friday in the journal Science.
Current and future efforts to reduce known environmental risk factors, they say, will have major impacts on cancer incidence in the U.S and abroad. But they say the new study confirms that too little scientific attention is given to early detection strategies that would address the large number of cancers caused by random DNA copying errors.
«These cancers will occur no matter how perfect the environment," Vogelstein says.
In a previous study authored by Tomasetti and Vogelstein in the Jan. 2, 2015, issue of Science, the pair reported that DNA copying errors could explain why certain cancers in the U.S., such as those of the colon, occur more commonly than other cancers, such as brain cancer.
In the new study, the researchers addressed a different question: What fraction of mutations in cancer are due to these DNA copying errors?
To answer this question, the scientists took a close look at the mutations that drive abnormal cell growth among 32 cancer types. They developed a new mathematical model using DNA sequencing data from The Cancer Genome Atlas and epidemiologic data from the Cancer Research UK database.
According to the researchers, it generally takes two or more critical gene mutations for cancer to occur. In a person, these mutations can be due to random DNA copying errors, the environment, or inherited genes. Knowing this, Tomasetti and Vogelstein used their mathematical model to show, for example, that when critical mutations in pancreatic cancers are added together, 77 percent of them are due to random DNA copying errors, 18 percent to environmental factors (such as smoking), and the remaining 5 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 note, 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 estimate that 66 percent of cancer mutations result from copying errors, 29 percent can be attributed to lifestyle or environmental factors, and the remaining 5 percent are inherited.
The scientists say their approach is akin to attempts to sort out why «typos» occur when typing a
«You can reduce your chance of typographical errors by making sure you’re not drowsy while typing and that your keyboard isn’t missing some keys," Vogelstein says. «But typos will still occur, because no one can type perfectly. Similarly, mutations will occur, no matter what your environment is, but you can take steps to minimize those mutations by limiting your exposure to hazardous substances and unhealthy lifestyles.»
Tomasetti and Vogelstein’s 2015 study created vigorous debate from scientists who argued that their previously published analysis did not include breast or prostate cancers, and it reflected only cancer incidence in the United States.
Tomasetti and Vogelstein now report a similar pattern worldwide, however, supporting their conclusions. They reasoned that the more cells divide, the higher the potential for
Tomasetti says these random DNA copying errors will only get more important as societies face aging populations, prolonging the opportunity for our cells to make more and more DNA copying errors. And because these errors contribute to a large fraction of cancer, Vogelstein says that people with cancer who have avoided known risk factors should be comforted by their findings.
«It’s not your fault," says Vogelstein. «Nothing you did or didn’t do was responsible for your illness.»
In addition to Tomasetti and Vogelstein, Lu Li, a doctoral student in Tomasetti’s laboratory in the Department of Biostatistics at the Johns Hopkins Bloomberg School of Public Health, also contributed to the research.