Most cancer mutations result from DNA copying errors

Most cancer mutations result from DNA copying errors

Most cancer mutations result from DNA copying errors

"The main objective of the new paper is to try, for the first time, to calculate how many of these mutations found in cancers are due to the environment, heredity or random mutations", Vogelstein said.

In 2015, Vogelstein and his colleague Christian Tomasetti turned convention on its head when they presented evidence that random mutations were a third, primary driver of cancer in addition to environment and hereditary.

Approximately 40% of cancers can be prevented by avoiding unhealthy environments and lifestyles, so public education should still focus on avoiding these environmental agents. In fact, while many scientists have long held that inherited mutations or damage from smoking or exposure to toxins were behind most cancers, the new study suggests that as many as two-thirds of cancer cases are the result of random and often tiny mistakes in DNA.

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. The team assumed the existing, largely agreed-upon idea that around three mutations are introduced into the genome every time a noncancerous, normal human stem cell divides. "They occur in junk DNA, genes unrelated to cancers, unimportant places with respect to cancer". His own 2015 research concluded they account for 10 to 30 percent of cancer cases. On the report, the researchers found a strong correlation the number of stem-cell divisions and the incidence of the disease.

The researchers estimate that 66% of cancer mutations result from copying errors, 29% can be attributed to lifestyle or environment, and the remaining 5% are inherited.

"Despite the role of the random replication component in producing mutations, you could still reduce the cancer risk hugely, for many types of cancer, by getting rid of the environmental and/or hereditary causes", he said.

He added that people who develop cancer despite avoiding known risk factors should not feel guilty, based on the study's findings.

Cancer can be caused by tobacco smoke or by an inherited trait, but new research finds that most of the mutations that lead to cancer crop up naturally. "Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention", Science, doi:10.1126/science.aaf9011, 2017.

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Random mutations occur all the time, but their effect varies with the affected gene, Vogelstein said in a press conference Wednesday.

"We're not saying the only thing that determines the seriousness of the cancer, or its aggressiveness, or its likelihood to cause the patient's death, are these mutations", said Vogelstein. With each spin, or cell division, a different combination of all three factors could affect the result, and each type of cancer, in a sense, is weighted with odds.

"Environmental exposures can influence cancer risk in many ways", he said, including whether cells fix cancer-causing mutations and whether the immune system destroys tumor cells before they cause actual disease.

The "Why me?" reaction that can come after a cancer diagnosis may have no easy answer, with new research showing that most tumors are caused by random genetic "mistakes".

But a third cause - random mistakes - actually accounts for two-thirds of these mutations, said the new study, published today (March 23) in the journal Science.

"We are already curing 68 per cent of people (with cancer)", Prof Aranda said.

Scientists have found that random DNA mutations cause most of the cancers. Right now, Vogelstein emphasizes, we don't know enough about what causes the random mutations to suggest that people take preventative measures, and there are likely a certain percentage of random mutations that are simply unavoidable. All but that last 20 percent of cases are preventable, at least in theory, Tomasetti says, because eliminating even one of the environmental mutations would have meant that the cancer did not develop.

The method the authors used is sound, says Noble, although they did have to rely on a number of assumptions to simplify the analysis.

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