Sunday, 30 April, 2017

Most cancerous mutations are random DNA errors

Teenager Ethan Smith-Garcia Image Caption Teenager Ethan Smith Garcia was given the chance to have precision therapy in the US
Tracy Craig | 30 March, 2017, 01:49

"Every time a perfectly normal cell divides it makes several mistakes - mutations", Vogelstein said. "Now most of the time, these mutations don't do any harm".

This time around, the duo analysed mutations involved in 32 types of cancer to estimate that 66 per cent of the gene flaws are due to random copy errors. Vogelstein and Tomasetti found that in lung cancer, 65 percent of mutations are caused by environmental factors, including smoking and air pollution, while 35 percent stem from random transcription errors. Environmental factors, like smoking and chemical exposure, account for 29 percent of cancerous mutations, according to the study. Only 5 percent was due to heredity or inherited complications.

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. This time around, the team used a "new mathematical model" to evaluate 32 cancer types, relying on worldwide data.

Researchers at John Hopkins University studied health records from 69 countries to establish the relationship between cell division and the risk of 17 types of cancer.

Tomasetti and Vogelstein conducted the new study described in a report published March 24 in the journal Science.

Studies have always attributed external factors behind cancer. "I consider this a completely new result compared to our previous one". The scientists calculated the percentage of cancers according to causes. This means healthy lifestyle choices still play a large part in preventing cancer. But only 0.2 percent of people get cancer of the small intestine, where cells divide fare less frequently.

The overlap was nearly exact, suggesting that cancers in tissues with high rates of cellular turnover - including brain, kidney, colon and liver - were far more common than could be explained by inherited or environmental factors. "But the difference in cancer rates in different tissues can still be the result of different underlying rates of cell division".

The remaining 66 percent of genetic mutations known to give cancer a foothold are random transcription errors in DNA, the pair concluded.

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With the help of mathematics, Vogelstein and Tomasetti were able identify how often these random mutations occur.

The scientists say their approach is akin to attempts to sort out why "typos" occur when typing a 20-volume book: being exhausted while typing, which represents environmental exposures; a stuck or missing key in the keyboard, which represent inherited factors; and other typographical errors that randomly occur, which represent DNA copying errors.

Despite the improvements to their methods, the team's recent findings have already been subjected to criticism. Dr. To that end, other scientists suggest that we must study the interplay of other factors, such as hormones, with genetic mutations to get a better understanding of the whole picture.

"This paper certainly won't be the last word on these matters", said Kevin McConway, emeritus professor of applied statistics at The Open University.

It's also important to note that Tomasetti and Vogelstein's conclusions do not imply that cancer prevention is pointless.

Vogelstein concurred, stressing that the latest research is "in ideal accord with epidemiological estimates that 42 percent of cancers can be prevented - and everyone should adhere to those prevention guidelines".

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.

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