Smokers experience one mutation to their DNA for every 15 cigarettes they smoker, according to a study that mapped out the genetic blueprint of a lung cancer patient. British researchers led the massive international project, which identified 23,000 mutations that bore the expected signs of damage caused by chemicals in tobacco smoke.
All cancers are caused by mistakes in the genetic code – mutations in DNA that can be triggered by environmental agents.
The scientists hope the results will help them understand the causes of cancer and to develop new treatments.
They found the genetic defects ranged from single-letter changes in the person’s code to deletions or re-arrangements of hundreds of thousands of letters.
No single mutation stood out as being the primary cause of the disease. Instead most were ‘passenger’ mutations that appeared to influence the development of cancer only in combination.
Study leader Dr Peter Campbell, from the Wellcome Trust Sanger Institute in Cambridgeshire said: ‘The knowledge we extract over the next few years will have major implications for treatment.
‘By identifying all the cancer genes we will be able to develop new drugs that target the specific mutated genes and work out which patients will benefit from these novel treatments.’
Dr Andy Futreal, also from the Wellcome Trust, said: ‘Cancers occur when control of cell behaviour is lost – cells grow how, when and where they shouldn’t.
‘Mutations in DNA caused by, for example, cigarette smoke are passed on to every subsequent generation of daughter cells, a permanent record of the damage done.
‘Like an archaeologist, we can begin to reconstruct the history of the cancer clone – revealing a record of past exposure and accumulated damage in the genome.’
A person’s risk of lung cancer is known to fall to around normal some 15 years after quitting smoking.
Scientists suspect that lung cells containing harmful mutations are replaced by new cells that are clear of defects.
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The researchers carried out the sequencing 60 times for lung cancer in order to produce accurate results. They also mapped the blueprint for melanoma (a dangerous form of skin cancer).
Professor Mike Stratton, joint head of the Cancer Genome Project said: ‘These are the two main cancers in the developed world for which we know the primary exposure.
‘For lung cancer, it is cigarette smoke and for malignant melanoma it is exposure to sunlight. With these genome sequences, we have been able to explore deep into the past of each tumour, uncovering with remarkable clarity the imprints of these environmental mutagens on DNA, which occurred years before the tumour became apparent.
‘We can also see the desperate attempts of our genome to defend itself against the damage wreaked by the chemicals in cigarette smoke or the damage from ultraviolet radiation. Our cells fight back furiously to repair the damage, but frequently lose that fight.’
Sir Mark Walport, director of the Wellcome Trust, said: ‘We want to drive healthcare through better understanding of the biology of disease.
‘This is the first glimpse of the future of cancer medicine, not only in the laboratory, but eventually in the clinic. The findings from today will feed into knowledge, methods and practice in patient care.’