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Smokers May Have Genetic Variation That Keeps Them From Quitting

by Lynn Shapiro, Writer | August 13, 2008

The researchers point out that the genetic variant explains only a portion of human smoking behavior, and that a more complete explanation of why people smoke and why they can't quit will require much more information about how genes interact with social influences and other environmental factors.

Pomerleau predicts that the ability to link behavioral patterns in smoking to individual genotypes will need extensive information concerning behavior, genes, and the environmental context -- as well as bioinformatic tools to bring it all together. "Understanding the genetics of complex disorders such as nicotine addiction will require much more research on key traits," he says.

The team notes that the CHRNA5 relationships appear to be strong and that practical applications from this research include new genetic tests for smoking risk and the development of medications that target smoking-risk genes.

Pomerleau states that the new paper builds on findings reported last year by fellow author Laura Bierut, in which a whole-genome study found that the same single nucleotide polymorphism, rs16969968, of the CHRNA5 gene was associated with smokers' level of nicotine dependence.

He also notes that, this year, three papers published independently of one another demonstrated that variations in the same gene, and related genes, greatly increase the risk of lung cancer.

Taking into account its links to increased liking of initial smoking, stronger likelihood of getting addicted to nicotine, and greater probability of developing lung cancer, this genetic variant may well constitute a "triple whammy" for smoking-related disease, he says.

A mechanism for explaining increased disease risk, proposed by one of the cancer genetics researchers, is the possibility that certain chemicals, for instance N-nitrosonornicotine in tobacco smoke, act on nicotine receptors in the lung to produce cancer-causing changes -- a process known as tumorigenesis.

The new findings linking first smoking experiences, smoking habits, and genetic variation build on previous research by Ovide Pomerleau and Cynthia Pomerleau, Ph.D., at U-M. In studies conducted over a 10-year span, they documented a link between nicotine-dependent smoking and positive first smoking experiences.


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