Study: Genetics Factor into Nicotine Metabolism, Smoking Levels, and Cancer Risk

A recent paper on genetics in the journal PLOS ONE offered more clues regarding why smokers quit or continue smoking. A single nucleotide polymorphism (SNP), pronounced “snip,” is a variation of a gene that can influence the gene’s effects. The study showed that two SNPs of the CYP2A6 gene determine the rate at which smokers metabolize nicotine, the addictive agent in tobacco products.

Both of these SNPs were associated with how heavily a person smoked. Status on one of these SNPs also significantly predicted whether a smoker would be able to quit smoking when s/he used bupropion as the quit-smoking medication. Thus, if the CYP2A6 gene caused faster nicotine metabolism, it also caused the person to smoke more, and to be less able to quit (at least when using bupropion, but there was a trend for this to be true of nicotine-replacement medication as well).

Finally, because “high risk” status on one of these CYP2A6 SNPs makes it harder for smokers to quit, it would make sense for this to increase a smoker’s risk of lung cancer. Indeed, in a post-hoc meta-analysis of four case-control studies, status on one of the two CYP2A6 SNPs (rs1137115) was significantly associated with lung cancer.

The paper was written by Andrew Bergen and co-authored by several colleagues, including UW-CTRI Research Director Dr. Tim Baker. The paper used data from three UW-CTRI studies to reach its conclusions.

“In sum, there are now two genes—CYP2A6 and CHRNA5—that have been shown to be associated with smoking heaviness, ability to quit smoking, and risk of lung cancer,” Baker said. “Other research suggests that these genes have independent effects on these outcomes. This research adds to our knowledge of factors that affect tobacco dependence and use, and that increase the risk of tobacco-related harms.”

Bergen AW, Michael M, Nishita D, Krasnow R, Javitz HS, Conneely KN, Lessov-Schlaggar CN, Hops H, Zhu AZ, Baurley JW, McClure JB, Hall SM, Baker TB, Conti DV, Benowitz NL, Lerman C, Tyndale RF, Swan GE. Drug Metabolizing Enzyme and Transporter Gene Variation, Nicotine Metabolism, Prospective Abstinence, and Cigarette Consumption. PLOS ONE. 2015 July 1;10(7):e0126113.