Scientists 'home in' on lung cancer genes that increase smokers' risk

Cancer Research UK

Cancer Research UK funded scientists 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, 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 per cent. Current or former 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."

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."

ENDS

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Notes to Editor

*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.

This study is one of three papers in Nature and Nature Genetics this week about genetic predisposition to lung cancer. For more information contact the Nature press office on 0207 843 4562 or email press@nature.com

The genetic material from the UK was collected in the Genetic Lung Cancer Predisposition Study (GELCAPS) by Professor Tim Eisen from the University of Cambridge, with Professor Houslton. This involved around 8,000 people in the United Kingdom and was supported by the National Cancer Research Institute (NCRI) Lung Clinical Studies Group.

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. Lung cancer rates for UK men have decreased by more than 40 per cent in the last thirty years reflecting the decrease in smoking rates in men since the mid-1970s. Female lung cancer rates in the UK have increased by more than 50 per cent in the last thirty years due to the increase in smoking rates in women.

There are over 38,300 new cases of lung cancer in the UK each year. Each year more than 33,000 people die from the disease.

Lung cancer is the most common cancer in the world with 1.3 million people diagnosed every year. Worldwide, the highest rates of lung cancer in men are currently in the regions of Central and Eastern Europe, and for women in Northern America.

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.

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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.

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