Smoking 15 cigarettes harms your DNA

 

Smokers experience one mutation to their DNA for every 15 cigarettes they smoke, 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.

Theyfound the genetic defects ranged from single-letter changes in theperson's code to deletions or re-arrangements of hundreds of thousandsof letters.

No single mutation stood out as being the primarycause of the disease. Instead most were 'passenger' mutations thatappeared to influence the development of cancer only in combination.

Study leader Dr Peter Campbell, from the Wellcome Trust SangerInstitute in Cambridgeshire said: 'The knowledge we extract over thenext 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.

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.'

The team's results have been published in two papers today in the journal Nature.

Smoking affects the human genome - a complete set of DNA in a person, including all genes - in the form of DNA methylation, finds a new study published in an American Heart Association journal Circulation: Cardiovascular Genetics. Some DNA methylation sites have been found to persist even after 30 years of quitting.

Smoking-associated DNA methylation sites were linked to more than 7,000 genes, or one third of known human genes.

DNA methylation is a process by which cells control gene activity, and it often modifies the function of genes. Scientists have found that DNA methylation could reveal a person's smoking history, and as a result, they could develop targeted new therapies for diseases associated with smoking.
"These results are important because methylation, as one of the mechanisms of the regulation of gene expression, affects what genes are turned on, which has implications for the development of smoking-related diseases," says Dr. Stephanie J. London, last author and deputy chief of the Epidemiology Branch at the National Institute of Environmental Health Sciences - part of the National Institutes of Health.
"Equally important is our finding that even after someone stops smoking, we still see the effects of smoking on their DNA," she adds.
Cigarette smoking is a significant modifier of DNA methylation. Research has uncovered genes associated with smoking that contribute to the development of smoking-related diseases. DNA methylation is also a potential link between smoking and cancer, as well as prenatal cigarette smoke exposure and the development of chronic diseases in adults.
An estimated 40 million adults in the United States currently smoke cigarettes. Cigarette smoking is regarded as the leading cause of U.S preventable disease and death, accounting for more than 480,000 deaths every year. More than 16 million Americans live with a smoking-related disease.
Despite smoking rates declining in many countries worldwide as a result of smoking campaigns and legislative action, even decades after people quit smoking, former smokers are at a long-term increased risk of diseases that include some cancers, chronic obstructive pulmonary disease, and stroke.
The molecular mechanisms behind these long-term effects are unclear. However, previous research has linked DNA methylation sites with genes connected to coronary heart disease and pulmonary disease, which suggests DNA methylation may play a role.
Researchers analyzed blood samples from almost 16,000 participants from 16 groups included in the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE) Consortium, including a group from the Framingham Heart Study that researchers have followed-up since 1971.

Common methylation sites linked to cardiovascular diseases, cancers

Compared with lifelong nonsmokers, the team found that DNA methylation sites associated with smoking were linked to more than 7,000 genes - accounting for one third of known human genes.
Findings suggest that the majority of DNA methylation sites in former smokers returned to levels observed in never smokers within 5 years of smoking cessation. However, some DNA methylation sites remained even 30 years after stopping smoking.
The most common DNA methylation sites detected were linked to genes associated with a greater risk of smoking-related diseases, such as cardiovascular diseases and certain cancers.
Investigators indicate that the long-term DNA methylation sites may emphasize genes that could put former smokers at risk of developing certain diseases years, even decades after quitting. This discovery could lead to researchers developing biomarkers to assess smoking history, which may result in new treatments emerging that could potentially target the methylation sites.

"Our study has found compelling evidence that smoking has a long-lasting impact on our molecular machinery, an impact that can last more than 30 years."

Roby Joehanes, Ph.D., Harvard Medical School

"The encouraging news is that once you stop smoking, the majority of DNA methylation signals return to never smoker levels after 5 years, which means your body is trying to heal itself of the harmful impacts of tobacco smoking," Joehanes concludes.
Read about how smoking thickens the heart wall and reduces the ability of the heart to pump effectively.

Written by Hannah Nichols