Smokers develop 150 mutations per lung cell

For the first time scientists have quantified the number of mutations caused by the number of cigarettes smoked in a lifetime.

Tobacco smoke causes mutations at the DNA level, and understanding these changes could provide new clues to how cancer develops and how to prevent it.

'This study offers fresh insights into how tobacco smoke causes cancer,' said Dr Ludmil Alexandrov, the co-first author of the study and theoretical biologist at Los Alamos National Lab, New Mexico. 'Tobacco smoking damages DNA in organs directly exposed to smoke as well as speeds up a mutational cellular clock in organs that are both directly and indirectly exposed to smoke.'

The study, published in Science, was carried out by scientists at the Los Alamos National Laboratory, New Mexico, and the Welcome Trust Sanger Institute, Cambridge. The team analysed DNA mutations in the genome sequences of 5243 smoking-related cancer tumours and compared them with genomes of non-smokers, using pattern-recognition software.

On average, smoking one packet of cigarettes a day over a lifetime causes 150 mutations in each lung cell, 97 mutations in each larynx or voice box cell, 23 mutations in each mouth cell, 18 mutations in each bladder cell, and six mutations in each liver cell, every year.

'For every 150 mutations in the cell each year, that is 150 opportunities for lung cancer to develop,' Dr David Gilligan, consultant oncologist at Papworth Hospital, who was not involved in the study, told the BBC.

Over 70 chemicals contained in tobacco create mutations at random places in the DNA. While some changes may be harmless, some are in places that are associated with cancer. The more a person smokes, the higher their risk of acquiring a mutation in a cancer-causing area in the DNA.

'You can really think of it as playing Russian roulette,' Dr Alexandrov told the Guardian. 'You can miss the right genes. But if you smoke you still play the game. It's a very strong message for people not to start smoking. If you smoke even a little bit you'll erode the genetic material of most of the cells in your body.' 

The study also found that tobacco smoke found its way to different organs not directly exposed to smoke, including bladder, kidneys and pancreas, and increased their 'molecular clock' – the natural mutation rate. This also increased the risk of cancer in those organs.

Smoking accounts for more than a quarter of cancer-related deaths in in the UK and is the most preventable cause of cancer in the world.

Los Alamos Director Charlie McMillan called the research 'a creative breakthrough in cancer research' which brought together Big Data generated by international cancer consortia and the supercomputing facilities at Los Alamos to address a leading public health issue.