Could a doctor someday use a smoker’s genetics to tailor treatments? We’re not there yet, but researchers are working on it, if only in the early stages.

Dr. Li-Shiun Chen of Washington University in St. Louis is leading a clinical trial, funded by a grant from the National Institute on Drug Abuse, that:

  1. Tests combination nicotine-replacement therapy (NRT) and varenicline to help smokers quit.
  2. Links the results with genetic variants determined in previous research.
UW-CTRI Research Director Dr. Tim Baker is collaborating. As of now, no researcher has published a genetics paper examining the two most effective cessation medications within the same study. In this new genetics study, researchers will stratify quit-smoking treatments (combo NRT, varenicline, or placebo) to ensure that the critical gene, CHRNA5, is equally represented across treatment groups. 

“CHRNA5 is the gene that has shown the strongest relations with smoking cessation,” Baker said. “There is also some promising evidence that it is fairly strongly related to NRT effects on cessation.”

Data show that if a person has a “risk variant” for CHRNA5 they benefit from NRT; however, if they do not have such a variant, they do not benefit. The new study will test whether this effect holds true in a larger trial.

“If this relation is strongly replicated,” Baker said, “it would suggest that, in clinical practice, people without risk variants would not get NRT, but other people would.”

Other important aims of this work are to: 
  1. Determine whether varenicline helps individuals without the risk variants.
  2. Explore how another key gene, CYP2A6, is related to treatment success. Does it inform treatment success beyond CHRNA5 status alone?
  3. Test whether CHRNA5 or CYP2A6 status helps predict adverse events and adherence to treatment.
At this point, tailoring treatments based on a smoker’s genetics is an unrealized goal. But the results from this study could nudge the research community a step closer to making it someday a reality.