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Brussels, 3 April 2008

Smoking genes? European scientists discover the first case of a genetic dependence to nicotine

Scientists from an EU-supported consortium have discovered that a mutation in a human gene confers nicotine dependence. They have shown that a particular variant of a nicotine-receptor gene impacts smoking behaviour and hence confers a 30% increase in risk of lung cancer and a 20% increase in risk of peripheral artery disease (PAD), a common and debilitating constriction of the arteries to the legs. Roughly half of the people of European descent carry at least one copy of this genetic variant, which does not influence smoking initiation, but makes it more difficult to quit. The results stem out from the European project GENADDICT (Genomics, mechanisms and treatment of addiction), which is supported by 8.1 million euros' worth of funding from the EU’s Sixth Framework Programme for research and by the U.S. National Institutes of Health.

"This breakthrough has been achieved thanks to the expertise and dedication of European researchers but also because more and more European scientists are working together. The European Union has been supporting health research for more than 20 years and we see clearly the benefits arising from these collaborations. This effort complements other related policies sponsored by the European Commission in the area of public health," said the European Commissioner for Science and Research, Janez Potočnik.

Cigarette smoking is a major public health problem. Tobacco is the single largest cause of avoidable death in the European Union, accounting for over half a million deaths each year. It is estimated that 25% of all cancer deaths and 15% of all deaths in the Union can be attributed to smoking. While the health risks of smoking are well known, relatively little is known about why some people are particularly likely to get hooked on cigarettes and may consequently be at greater danger of lung cancer and other diseases.

Nicotine dependence is believed to be the main reason for continued smoking. GENADDICT aims to identify the genes involved in this and other addictions by bringing together leading European public and private research organisations. It is an integrated multidisciplinary project that connects human genetics research in addicted patients with genomic studies of mice.

GENADDICT is a major collaboration between 12 teams across 7 European countries, including 2 new Member States (Hungary and Poland) and 1 associated country (Iceland). The consortium includes an SME developed from the research success of one of the partners. The teams belong to the following organisations: University of Surrey (UK, coordinator), University Pompeu Fabra (ES), CNRS (FR), INSERM (FR), Life & Brain GmbH (DE), the Polish Academy of Sciences (PL), the Hungarian Academy of Sciences (HU) and deCODE genetics (IS), which is the main contributor to the results presented today.

The mutation which contributes to nicotine addiction is located on chromosome 15q24 and affects one nicotine-acetylcholine receptor in the brain. A study of 11,000 Icelandic smokers participating in the research showed that the mutation is more common in heavier smokers than in smokers overall and in the general population. It was also correlated with likelihood of clinical diagnosis of nicotine dependence. Comparisons between current and past smokers showed that people carrying this variant tend to smoke more and are less likely to quit smoking. Interestingly, the variant is less common among smokers who smoked less than 10 cigarettes per day than it is among non-smokers, supporting the notion that the mutation does not influence smoking initiation, but rather confers risk of nicotine dependence among those who start. The gene was then analyzed in a total of 32,000 patients and controls from Iceland, New Zealand, Austria, Sweden, Italy, the Netherlands and Spain for lung cancer and PAD.

The results, published today in the scientific journal Nature, are a milestone in the identification of genetic risk factors and genes involved in addiction. Addiction is a brain disease, common in Europe, but there has been little advance in the drug treatment for addiction over the last 20 years. In addition to studying nicotine addiction, the GENADDICT consortium is investigating alcohol and drug dependence.

Addiction can come in many forms. Some people are addicted to a substance, such as tobacco, alcohol, drugs or illegal narcotics like heroin and cocaine. Others may have behavioural addictions not involving a substance per se, such as gambling, eating disorders and obsessive compulsions. Although the role of genetics in addiction has been recognised for some time, tracking down the guilty genes is not easy. This is in part because addiction itself varies widely and can be exacerbated by familial and environmental influences, making isolating the responsible genes a huge challenge.

Through understanding the genetics of addiction the GENADDICT research may give new insight into its biological basis, and into the dysfunction of the addicted brain. It is likely to boost the development of new treatments and strategies against this serious disease.

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