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Genetic link to smoking addiction

Cigarettes
Cigarettes may interact with our genes

Scientists have identified genetic variations that raise the risk of lung cancer for smokers and former smokers.

And there is also some evidence to suggest that they may make carriers more addicted to tobacco.

Three research teams, writing in the journals Nature and Nature Genetics, each pinpointed two key areas of variation on chromosome 15.

The variants are common in the population - but they only raise lung cancer risk in those who have smoked.

Current or former smokers who carry two copies of both variants, one from each parent - about 15% of the total - have a raised risk of 70-80%.

Those who carry one copy of each variant have a raised risk of around 28%.

LUNG CANCER
Second most common form of cancer in the UK after breast cancer
Smoking and passive smoking cause nine out of ten lung cancers
Half of all smokers eventually die from lung cancer or another smoking-related illness. And a quarter of smokers die in middle age - between 35 and 69.
There are over 38,300 new cases, and more than 33,000 deaths from lung cancer in the UK each year
Men are more likely to be affected, although the number of women with lung cancer has been increasing

The researchers differ on exactly how the key variants influence lung cancer risk.

A team from Icelandic company deCODE Genetics - which carried out the largest of the studies - say their work suggests that carrying the variants makes people more addicted to tobacco once they start smoking.

But an international team, including scientists from the Institute of Cancer Research, the University of Cambridge and Johns Hopkins University in Baltimore, believe it is more likely that the variants interact directly with tobacco to cause lung cancer.

This may be by increasing the likelihood that nicotine will trigger the uncontrolled cell division associated with cancer.

All the researchers agree the work is a major step forward in identifying people at risk for non-small cell lung cancer - which makes up 80% of all lung cancer cases.

Thousands studied

Each of the research groups studied the DNA of thousands of current and former smokers, but each worked with a different sample, atlhough all were people of European descent.

However, they all found that a particular pattern of gene variation at two points of chromosome 15 was more common among people who developed lung cancer, than among those who remained healthy.

It is unclear whether the key set of variations affect just one gene, or three closely connected genes.

Dr Lesley Walker, of the charity Cancer Research UK, said: "We know that smoking greatly increases the risk of lung cancer - causing nine out of ten cases of the disease.

"This research tells us there are some smokers who are even more vulnerable to lung cancer because of their genetic profile."

Professor Chris Amos, from the MD Anderson Cancer Center, and lead author of one of the studies, warned that lung cancer was a complex condition.

"There are so many different cancer-causing compounds in tobacco smoke that it is hard to separate them and we don't fully understand the mechanisms that cause lung cancer."

Smokers who do not have the variants are still more than 10 times more likely to get lung cancer than people who have never smoked, whose risk is less than 1%.


SEE ALSO
Lung Cancer
30 Jan 04 |  Medical notes

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