A mutation with every pack - cancer genes unravelled

Thursday December 17th, 2009

A typical smoker acquires one genetic mutation for every 15 cigarettes smoked, according to ground-breaking research published last night.

Scientists unveiled detailed genetic studies of two major cancers, lung cancer and the skin cancer melanoma.

The works paints a picture of the changes that lead to each cancer, mutation by mutation.

In the case of lung cancer, it has enabled scientists to track the damage caused by cigarettes.

And the work on melanoma has showed how over exposure to the sun and ultra-violet light can trigger cancer.

The research, published in the journal Nature, shows that more than 23,000 mutations lead to lung cancer. Researchers said the genome was "ravaged" by mutations.

Researcher Dr Peter Campbell, of the Wellcome Trust Sanger Institute, said: "The profile of mutations we observed is exactly that expected from tobacco, suggesting that the majority of the 23,000 we found are caused by the cocktail of chemicals found in cigarettes.

"On the basis of average estimates, we can say that one mutation is fixed in the genome for every 15 cigarettes smoked."

Researchers said they hoped the work would lead to details of the chemicals that cause lung cancer, including those that trigger disease in people who do not smoke.

The second piece of research shows some 33,000 mutations leading to melanoma.

Dr Campbell said: "It is amazing what you can see in these genomes. UV-light-induced mutations leave a typical signature, forming the vast majority of the mutations.

"Indeed because of the clarity of the genome data, we can distinguish some of the early, UV-induced mutations from the later mutations that do not have this signature, presumably occurring after the cancer cells spread from the skin to deeper tissues."

The findings were welcomed by Cancer Research UK.

Chief executive Harpal Kumar said: "This fascinating work shows that great progress is being made to understand a lot more about how cancer develops.

"It shows in precise detail, and for the first time, the huge impact that smoking has in triggering the development of lung cancer, as well as the extent of the damage caused by UV radiation in relation to melanoma.

"The next step will be to find out which of these thousands of mutations are just 'collateral damage' and which actually drive these cancers. Only then can we begin to find ways to correct or prevent them."

* Meanwhile British regulators have warned they will not back a new drug aimed at extending the lives of patients with lung cancer.

The drug pemetrexed has been proposed for "maintenance" treatment for non small cell lung cancer - but the National Institute for Health and Clinical Excellence said there were too many uncertainties about the evidence backing it.

Dr Carol Longson, of NICE, said: "In September NICE recommended pemetrexed as a first line treatment for non-small-cell lung cancer and we are disappointed not to have been able to recommend the drug as a maintenance treatment as well."

Hilary Tovey, of Cancer Research UK, said it hoped the problems could be resolved "so that this negative decision can be turned into positive action which will benefit cancer patients in the future."

Nature 2009 doi:10.1038/nature08629, doi:10.1038/nature08658

Tags: Cancer | Dermatology | Drug and Alcohol Abuse | Respiratory | UK News

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