Gene May Increase Risk of Smoking

In a paper published online in the journal Addiction, a multi-university collaborative team of researchers specializing in statistical genetics, gene analysis, and trait analysis reports an association between a variant in the CHRNA5 nicotine receptor gene, initial smoking experiences, and current smoking patterns. 

The genetic and smoking data come from 435 volunteers: never-smokers; those who smoked no more than 100 cigarettes in their lives and never formed a habit; and regular smokers who smoked at least 5 cigarettes a day for at least the past 5 years. The regular smokers in the study were far more likely than the never-smokers to have the less common rs16969968 form of the CHRNA5 gene, in which just one base-pair in the gene sequence was different from the more common form. This kind of genetic variation is called a single nucleotide polymorphism. Smokers were also 8 times as likely to report that their first cigarettes gave them a pleasurable buzz. 

“It appears that for people who have a certain genetic makeup, the initial physical reaction to smoking can play a significant role in determining what happens next,” said senior author and project leader Ovide Pomerleau, a psychiatry professor at the University of Michigan Medical School and founder of the U-M Nicotine Research Laboratory. He added that if smoking continues, nicotine addiction can occur in a few days or months. The finding of a genetic association with pleasurable early smoking may help explain how people get addicted. 

The researchers point out that the genetic variant explains only a portion of hu-man smoking behavior. Dr. 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. The team notes that the CHR-NA5 relationships appear to be strong and that practical applications from this re-search include new genetic tests for smoking risk and the development of medications that target smoking-risk genes. A mechanism for explaining increased disease risk, proposed by some cancer genetics researchers, is the possibility that chemicals such as N-nitrosonornicotine in tobacco smoke act on nicotine receptors in the lung to produce changes that cause cancer, a process known as tumorigenesis. There are 3 papers published independently this year that demonstrated that variations in the same gene and related genes greatly increase the risk of lung cancer.