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DNA 'mistakes' cause most cancers

25 March 2017

More than two-thirds of cancer-causing cell mutations are simply due to random and unpredictable DNA copying "mistakes", according to two US-based scientists. The study was conducted by the same group of researchers who carried out another study that was published in 2015 which blamed bad luck or random gene mutations for cancer.

Copying mistakes were linked to 77 per cent of pancreatic cancers but only 35 per cent of lung cancers, which were mostly triggered by smoking and other environmental factors.

"The main goal 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. There have been a lot of risk factors like family history and lifestyle habits but a new study reveals that most cancers might be a case of random DNA mutations.

In contrast, they noted, more than two-thirds of the mutations in lung cancer arise from environmental factors, mostly smoking.

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"The results we obtained are essentially the same", he said, and "they continue to suggest that there is an important correlation between the number of stem-cell divisions in an organ and the risk of cancer". While most are harmless, a small number affect genes that will promote cancer.

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.
Cancer prevention advocates anxious the idea might sway people to give up on healthier lifestyles. Those influences don't show up in genomic analyses like those the Hopkins researchers did but are affected by lifestyle and environmental factors, said Ross Prentice, a renowned cancer biostatistician at Fred Hutchinson Cancer Center in Seattle.

"We all agree that 40 percent of cancers are preventable", said Vogelstein. It's a finding that could change how researchers wage the "war on cancer", says study co-author Bert Vogelstein, a geneticist at the Sidney Kimmel Comprehensive Cancer Center in Baltimore, Maryland.

What causes cancer? High-profile culprits obviously include bum genes inherited from parents and harmful environmental and lifestyle factors, such as smoking or not wearing sunscreen. "With so numerous mutations caused by R, the internal enemies, one of the best strategies is to nip their attacks in the bud", Vogelstein said during a press conference announcing the results.

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At the press conference, Vogelstein said he hoped this research would offer comfort to millions of patients who have developed cancers despite living healthy lifestyles, helping them feel less guilty about contracting the disease since mutations are unavoidable.

"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. These factors can, in fact, cause cancer, but the third cause, random mutations, accounts for two-thirds of the disease. "But the data doesn't convince me".

The findings - which estimate that 66 percent of cancer mutations are effectively bad luck that we can't do anything about - support the conclusions of a controversial paper released in 2015 by the same researchers, which came under fire for appearing to suggest that there was nothing we could do to prevent various cancers.

The team at the Johns Hopkins Kimmel Cancer Center conducted a study to find out what fraction of mutations in cancer DNA copying errors are responsible for.

The misinterpretations sparked a blast of corrective pieces, opinions, and even new studies.

Inherited factors are also not known to play a role in lung cancers.

Certain cancers occur more often in certain areas than in others.

As it is the fact that mutation cannot be avoided and that cancer can take place even in a ideal environment, Dr. Vogelstein hopes that early detection should be the main focus.

DNA 'mistakes' cause most cancers