Quitting smoking is hard, and researchers at the University of Toronto and the Centre for Addiction and Mental Health (CAMH) have discovered one reason why: it’s in the genes.
Each smoker has a different genetic makeup, which influences their response to different treatments to help them quit. Now, these researchers plan to determine how to best personalize treatments to maximize the effectiveness of smoking cessation efforts.
Millions of adults in North America try to quit smoking every year, but the success rates of smoking cessation treatments vary widely. And there are no personalized approaches to helping smokers quit that have been translated into clinical practice.
The international study, led by Professor Rachel Tyndale at U of T and CAMH and Professor Caryn Lerman at the University of Pennsylvania, will investigate the pharmacogenetics of nicotine addiction treatment. It is backed by a $12-million (U.S.) grant through the National Institute of Health’s Pharmacogenomics Research Network initiative, a group of scientists from across North America focused on understanding how genes affect a person’s response to medicines.
Previous research led byTyndale identified a genetically informed marker that reflects individual differences in how quickly nicotine breaks down in the body. This biomarker can be used to predict the success of different smoking cessation treatments for individual smokers. The new study will determine how to translate this biomarker into clinical practice.
“This marker has the potential to help clinicians choose the best medication for people trying to quit, based on their genetics, and thus improve cessation response,” said Tyndale, a professor of pharmacology at U of T, and Canada Research Chair in Pharmacogenetics and head of pharmacogenetics for CAMH. “This is the first prospective randomized trial using a genetically informed biomarker to optimize smoking treatment on an individual level.”
The biomarker, referred to as the nicotine metabolite ratio (NMR), reflects genetic variation in the CYP2A6 gene, as well as environmental influences on nicotine metabolism. In this study, 1350 adult smokers will have their NMR assessed to determine whether they metabolize nicotine slowly or quickly. They will then be sorted into two groups – slow metabolizers and normal metabolizers – and randomized to treatment with either placebo, a nicotine patch, or Pfizer’s Chantix (varenicline). Each participant will also provide genetic material (DNA) which will be used to identify additional gene variants that may also contribute to the nicotine addiction treatment response. The prospective, double-blind placebo controlled trial will be completed within the next four years.