Date Published: 2 April 2008

Scientists focus on lung cancer genes that increase smokers' risk (Cancer Research)

Cancer Research UK

Cancer Research UK funded scientists have discovered the specific area of the genome containing one or more genes that can put smokers at even more risk of developing lung cancer. Their findings are published online in Nature Genetics.

The international team of researchers, jointly led by Professor Richard Houlston at The Institute of Cancer Research, carried out a 'whole genome search' for faulty genes that increase lung cancer risk. They studied the DNA – the genetic material that makes us unique – of thousands of men and women in the UK and the US. All of the people involved in the study were current or former smokers. Around half were lung cancer patients and the other half were healthy.

Initially they studied more than 300,000 'tags' – parts of our DNA that act as a 'roadmap' to our genes – in the patients and healthy people. Eventually they narrowed the search down to two 'tags', or genetic variants – within the region of the genome called chromosome 15 – which were more common among the lung cancer patients than the healthy people. These genetic variants have previously been implicated in lung cancer risk and roughly half the population carries either one or two copies of each.

Current or former smokers who carry one copy of each genetic variant increase their risk of lung cancer by 28%. Current or former smokers with two copies of each variant increase their risk by 80%. People who carry these variants, but have never smoked, are not at increased risk of the disease.

Professor Houlston said:

" We’ve found that these genetic variants are strongly associated with lung cancer. Both smokers and non-smokers have a fifty-fifty chance of carrying them but, significantly, they only increase the risk of lung cancer in people who have smoked."

Dr Lesley Walker, director of cancer information at 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."

Within the chromosome 15 region of the genome are two genes which may play a role in nicotine addiction, CHRNA3 and CHRNA5. The team investigated further to find out if the genetic variants have an indirect effect on lung cancer risk by affecting people’s smoking behaviour – making it more difficult for them to quit or need to smoke more, for example. The alternative possibility is that the genetic variants play a direct role in the development of the disease.

To find out which of these possibilities was the case, they compared the strength of the association in groups of people with different smoking behaviour. They found weak evidence that the number of cigarettes smoked each day or years a person has been a smoker, or being a former smoker rather than a current smoker, affected the strength of this association.

Professor Richard Houlston added:

" Although these results need to be confirmed in larger numbers of people, they suggest that the genes in this region of the genome interact directly with tobacco to cause lung cancer.

Further studies will also be needed to pinpoint specifically which gene, or genes, in this region are involved and to unravel the biology behind how they increase the risk of lung cancer."

The researchers used a multi-stepped approach to find the region of the genome linked to lung cancer. After they studied the initial 300,000 'tags', the tags which were more common among the lung cancer patients than the healthy people were then reassessed in new, larger groups of patients and healthy people.

After repeating the process for the 10 most significant tags, the team whittled them down to isolate just one key genetic region – 15q25.1 (chromosome 15).

Dr Lesley Walker added:

" It will be some time before we are able to identify who is most at risk of developing lung cancer, but when we do, this could help us discourage people from taking up smoking altogether. Stop Smoking services could also be more specifically tailored to this group, but all smokers would be strongly encouraged to quit, as they are still at high risk of developing a tobacco related disease.

It's important to remember that the best thing a smoker can do to reduce their risk of lung cancer and a host of other life-threatening diseases is to quit. "


Source: Cancer Research UK.

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