deCODE genetics, Inc. Shows How a Single Variant in the Sequence of the Genome Confers Nicotine Dependence and Risk of Lung Cancer
REYKJAVIK, Iceland, April 2, 2008 /PRNewswire-FirstCall/ -- Cigarette smoking is a major public health problem that contributes to millions of deaths around the world each year. While the health risks of smoking are well known, relatively little is known about why some people are particularly likely to get addicted to cigarettes and may consequently be at greater danger of lung cancer and other diseases.
Today scientists from deCODE genetics and their colleagues from several universities report in the journal Nature a clear link between a single-letter variant in the sequence of the human genome (SNP) and susceptibility to nicotine dependence. Moreover, in part because of this impact on smoking behavior, each copy of the risk variant of this SNP confers an approximately 30% increase in risk of lung cancer and a 20% increase in risk of peripheral arterial disease (PAD), a common and debilitating constriction of the arteries to the legs. Roughly half of people of European descent carry at least one copy of the variant, which the deCODE team estimates to account for some 18% of lung cancers and 10% of cases of PAD. These are also perhaps the highest-impact risk factors yet found for either condition. deCODE aims to apply these findings in the development of a DNA- based test which can be used to aid in personalizing and increasing the effectiveness of smoking cessation efforts, and of predicting risk of lung cancer and PAD.
The SNP, rs1051730, is located on chromosome 15q24 in a nicotine acetylcholine receptor called CHRNA3. The paper, 'A variant associated with nicotine dependence, lung cancer and peripheral arterial disease,' is published today in the online edition of Nature, at www.nature.com.
"These findings provide an example of the power of human genetics for shedding light on the most complex health challenges. Not only have we made a convincing link between a single SNP and a behavioral disorder -- greater smoking quantity and addiction to nicotine -- but also demonstrated how this risk factor translates into risk of lung cancer and PAD. This is an important advance that we will use in our diagnostics programs to develop means to enable individuals and their doctors to better understand and reduce the risk of smoking to their health. As of today we have also integrated this variant into our deCODEme(TM) personal genome analysis service," said Kari Stefansson, CEO of deCODE.
The deCODE team began this study with a smoking history questionnaire distributed to some 50,000 Icelanders, in which respondents were asked to say whether they had ever smoked, were still smokers, and, if so, how many cigarettes they smoked per day. More than 300,000 SNPs were then analysed in a subset of more than 10,000 smokers participating in deCODE's research, and the "T" version SNP rs1051730 was shown to be 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. 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 variant does not influence smoking initiation, but rather confers risk of nicotine dependence among those who start. The variant 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, two common diseases strongly associated with smoking.
deCODE gratefully acknowledges the participation of the patients and researchers from eight countries who took part in this study. This study was supported in part by funding from the European Commission (Grant Number: PL005166 GENADDICT) and from the National Institute of Drug Abuse of the U.S. National Institutes of Health (Grant Number: 5R01DA17932-3).
deCODE is a biopharmaceutical company applying its discoveries in human genetics to the development of drugs and diagnostics for common diseases. deCODE is a global leader in gene discovery -- our population approach and resources have enabled us to isolate key genes contributing to major public health challenges from cardiovascular disease to cancer, genes that are providing us with drug targets rooted in the basic biology of disease. deCODE is also leveraging its expertise in human genetics and integrated drug discovery and development capabilities to offer innovative products and services in DNA-based diagnostics, bioinformatics, genotyping, structural biology, drug discovery and clinical development. deCODE is delivering on the promise of the new genetics(SM). Visit us on the web at www.decode.com; on our diagnostics website at www.decodediagnostics.com; and, for our pioneering personal genome analysis service, at www.decodeme.com.
Any statements contained in this presentation that relate to future plans, events or performance are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially from those described in the forward- looking statements. These risks and uncertainties include, among others, those relating to technology and product development, integration of acquired businesses, market acceptance, government regulation and regulatory approval processes, intellectual property rights and litigation, dependence on collaborative relationships, ability to obtain financing, competitive products, industry trends and other risks identified in deCODE's filings with the Securities and Exchange Commission. deCODE undertakes no obligation to update or alter these forward-looking statements as a result of new information, future events or otherwise.
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