DeCODE scientists discover common SNPs that increase number of CPD and risk of lung cancer

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 http://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.