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'Homing In' on Lung Cancer Genes


Wednesday 2 April 2008

Scientists at The Institute of Cancer Research have pinpointed an 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 today (Wednesday) in Nature Genetics*.

The international team of researchers, jointly led by Professor Richard Houlston at The Institute of Cancer Research and funded by Cancer Research UK, 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. Around half the people they investigated were lung cancer patients who had smoked or were smokers (ever smokers), and the other half were ever smokers without lung cancer.


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 of these genetic variants.


Ever smokers who carry one copy of each of the genetic variant increase their risk of lung cancer by 28 per cent. Ever smokers with two copies of each variant increase their risk by 80 per cent. 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."


Within the chromosome 15 region of the genome are two genes – CHRNA3 and CHRNA5 – that may play a role in nicotine addiction, so the team investigated further. They wanted 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. Or whether the genetic variants play a direct role in the development of the disease.


To do this 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 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, 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. It will be some time before we are able to identify who is most at risk but when we do, this could help us discourage people from taking up smoking altogether and tailor stop smoking services to smokers who are more at risk of developing lung cancer.


"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."


- ends -


For further information, please contact:

Nadia Ramsey

The Institute of Cancer Research

0207 153 5359 / 07721 747900

[email protected]


Notes to editors:

*A genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Houlston, R. et al 2008. Nature Genetics XX YY.


Lung cancer

  • Lung cancer is the second most common form of cancer in the UK after breast cancer. Smoking and passive smoking cause nine out of ten lung cancers.
  • Men are more likely to be affected, although the number of women with lung cancer has been increasing. There are over 38,300 new cases of lung cancer in the UK each year
  • There are two types of lung cancer – non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). They are different because they originate in different types of cells in the lungs. Around 80% of lung cancer is NSCLC.

Smoking and risk of lung cancer

  • Smoking is the single biggest preventable cause of cancer in the world. It is responsible for nine out of ten cases of lung cancer in the UK, with smokers overall 26 times more likely than non-smokers to develop the disease.
  • 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.
  • The good news is that most of these deaths are preventable by giving up smoking in time.
  • The more cigarettes a person smokes a day, the higher their risk of cancer. But a person’s risk of cancer is increased even if they only smoke a few cigarettes a day. Light smoking can still endanger health.
  • Studies have shown that people who smoke 1–4 cigarettes a day are still almost three times more likely to die of heart disease and lung cancer than non-smokers.
  • Some scientists have found that the number of years a person smokes for affects their cancer risk more strongly than the number of cigarettes they smoke a day. For example, smoking one pack a day for 40 years is much more dangerous than smoking two packs a day for 20 years.
  • The best way to reduce the risk of cancer is to give up smoking completely.


About the Institute of Cancer Research

  • The Institute of Cancer Research is Europe’s leading cancer research centre with expert scientists working on cutting edge research. It was founded in 1909 to carry out research into the causes of cancer and to develop new strategies for its prevention, diagnosis, treatment and care. Website:
  • The Institute is a charity that relies on voluntary income. The Institute is one of the world’s most cost-effective major cancer research organisations with over 90p in every £ directly supporting research.


About Cancer Research UK

  • Together with its partners and supporters, Cancer Research UK's vision is to beat cancer.
  • Cancer Research UK carries out world-class research to improve understanding of the disease and find out how to prevent, diagnose and treat different kinds of cancer.
  • Cancer Research UK ensures that its findings are used to improve the lives of all cancer patients.
  • Cancer Research UK helps people to understand cancer, the progress that is being made and the choices each person can make.
  • Cancer Research UK works in partnership with others to achieve the greatest impact in the global fight against cancer.
  • For further information about Cancer Research UK's work or to find out how to support the charity, please call 020 7009 8820 or visit
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