Reykjavik, ICELAND, April 25, 2010 – Cigarette smoking is a major cause of illness and death worldwide. But it is a complex behavior, and how much people smoke, how hard they find it to quit, and the impact of long-term smoking on health varies greatly among individuals. A substantial portion of this variability is genetic. Two years ago, deCODE discovered the first common, single-letter variation (SNP) in the sequence of the human genome, on chromosome 15q25, associated with nicotine addiction and risk of lung cancer. Today, deCODE scientists and academic colleagues from 23 institutions in a dozen countries build on this work with the discovery of common SNPs on chromosomes 8p11 and 19q13 that among smokers increase the number of cigarettes smoked per day (CPD), a measure of nicotine addiction, and increase risk of lung cancer.
The study, published today in the online edition of Nature Genetics, analyzes detailed genotypic and smoking data from more than 130,000 participants. Both of the new SNPs are common, and in smokers each copy carried associates with a small increase in smoking quantity – about half a cigarrette per day – but an approximately 10% increase in risk of lung cancer compared to non carriers. This is about one third of the increase in lung cancer risk conferred by the SNP on chromosome 15q25. But taken together these variants can identify a sizeable proportion of smokers whose health is at even greater risk than average from their habit, information which may serve as an additional spur to smoking cessation. The study, ‘Sequence variants at CHRNB3-CHRNA6 and CYP2A6 affect smoking behavior,’ can be found at www.nature.com/ng.
“Smoking is bad for anyone’s health. It is even worse for some, and today’s discoveries continue to strengthen our ability to identify who those people are and give them a compelling additional reason to quit. We plan to incorporate these SNPs into our testing products to do that. What we do not yet know is exactly how this additional risk is conferred. To some degree these variants suggest that those for whom nicotine is more addictive are driven to smoke more, increasing their exposure to environmental risk. But given the quite substantial corresponding increases in risk of lung cancer it may also be that they make people more susceptible to the noxious effects of tobacco smoke. What is clear is that these variants — which are all near genes that encode nicotine metabolizing enzymes and receptors — are giving us a solid starting point for finding answers to advance personal and public health,” said Kari Stefansson, executive chairman and president of research at deCODE and senior author on the paper.
deCODE wishes to thank all those who participated in and contributed to this study. It was supported in part by the National Institutes of Health (R01-DA017932), and the European Comission’s GENADDICT project (LSHM-CT-2004-005166) and ENGAGE smoking consortium (HEALTH-F4-2007-201413).
Headquartered in Reykjavik, Iceland, deCODE genetics is a global leader in analyzing and understanding the human genome. Using its unique expertise and population resources, deCODE has discovered key genetic risk factors for dozens of common diseases ranging from cardiovascular disease to cancer. deCODE employs its capabilities to develop DNA-based tests and personal genome scans to better understand individual risk and empower prevention. It also licenses its tests, intellectual property and analytical tools to partners, and provides comprehensive genotyping, sequencing and data analysis services to companies and research institutions around the globe. Through its CLIA- and CAP-certified laboratory deCODE offers DNA-based tests for gauging risk and empowering prevention of common diseases, including deCODE T2™ for type 2 diabetes; deCODE AF™ for atrial fibrillation and stroke; deCODE MI™ for heart attack; deCODE ProstateCancer™ for prostate cancer; deCODE Glaucoma™ for a major type of glaucoma; and deCODE BreastCancer, for the common forms of breast cancer. Through its pioneering personal genome analysis service deCODEme™, deCODE enables individuals to better understand their risk of dozens of common diseases and to learn about their ancestry and other traits.