Causes of cancer may leave ‘fingerprints’ in DNA, scientists say

Cigarette butt

 Scientists may be able to find out what triggered a tumour’s formation by looking at genetic mutations. Photograph: Matt Morton/PA

From smoking to alcohol, air pollution to sunlight, a host of factors in our environment can cause cancer. Now scientists say they might be able to pinpoint the culprits for individual tumours.

Experts say they have managed to link particular environmental triggers with specific genetic mutations that give rise to cancer, opening up the possibility that researchers could look for clues in a tumour to deduce what triggered its formation.

“Mutational signatures are the fingerprints that carcinogens leave behind on our DNA and, just like fingerprints, each one is unique,” said Dr Serena Nik-Zainal, of the Medical Research Council cancer unit at Cambridge University, who co-led the research. “They allow us to treat tumours as a crime scene and, like forensic scientists, allow us to identify the culprit, and their accomplices, responsible for the tumour.”

Cancers develop as a result of changes to the DNA within cells. These changes – or mutations – can affect the way the cells divide and the growth of tissue, producing tumours. According to the latest figures, one in two people will develop cancer in their lifetime.

Writing in the journal Cell, researchers from the UK report how they exposed human stem cells, produced from skin cells, to 79 different chemicals or processes that are believed to cause cancer including solar radiation, various chemotherapy drugs and a host of substances found in tobacco smoke.

Overall, the team found 41 of these – or 52% of the agents – produced distinct genetic changes that could be spotted in cells, with some producing more than one hallmark. The team then compared these signatures with mutations seen in human cancers.

“We’ve used this technique to create the most comprehensive catalogue to date of the patterns of DNA damage produced by environmental agents across the whole human genome,” said Prof David Phillips of King’s College London. “It should allow us to examine a patient’s tumour and identify some of the carcinogens they have been exposed to that may have caused the cancer.”

The team found that the artificial sun produced a similar set of mutations to those seen in UV-associated cancers, while genetic signatures were also seen for a range of substances found in tobacco smoke, with these similar to those seen in lung cancers associated with smoking. They also found genetic changes produced by the chemotherapy drugs cisplatin and carboplatin were consistent with those seen in myeloid tumors that developed in people who had undergone chemotherapy.

Nik-Zainal said: “Our reference library will allow doctors in future to identify those culprits responsible for causing cancer. Such information could be invaluable in helping inform measures to reduce people’s exposure to potentially dangerous carcinogens.”

While the team said the approach could also flag previously unknown causes of cancer, they urged caution, noting it could also lead to the suggestion of exposure to a substance which has not actually been encountered. “This is important to stress as it may have important legal implications for industries where some of these agents may be occupational exposures,” they wrote.


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