Can't Quit Smoking? The Future May Bring Targeted Help
Using CPS-3 data, American Cancer Society researchers discover that the difficulty of quitting smoking may be ?related to newly identified genes.?
Association Between Genetic Variants and the Difficulty to Quit Smoking
This graph is a type of scatter plot, called a Manhattan plot, that scientists use to visualize results from a genome-wide association study (GWAS). Each point represents one of the millions of genetic variants. The x-axis shows the variant’s position on a chromosome. On the y-axis, higher points represent a stronger association between the genetic variant and a trait, feature, or disease being examined. In this example, the examined trait was people who find it difficult to quit smoking. Source: “A novel smoking cessation behavior based on quit attempts may identify new genes associated with long-term abstinence.” Addictive Behaviors, Oct. 2024
The Challenge
Most people who smoke know that quitting would lower their risk of developing and dying from a smoking-related disease. So, many want to quit.
In fact, every year about 50% of those currently using cigarettes try to quit. Unfortunately, only about 8% quit for good.
Many studies have tried to identify genetic variants that influence the ability to quit, such as variants linked with the number of cigarettes smoked, the age a person started smoking, and withdrawal symptoms.
For many previous studies, scientists compared current smokers with previous smokers, but these broad characteristics (known as a phenotype) weren't precise enough to discover the exact genetic variants specific to people who have a hard time quitting.
To accurately assess the ability to quit smoking, the studied phenotype needs to include both current and former smokers who have tried to quit at least once.??
To improve the identification of genetic variants related to quitting smoking, American Cancer Society (大象tv) researchers led??using new sets of characteristics related to the extremes of quit attempts:
- At one end: Easy quitters who stopped smoking for at least 1 year after only one attempt.?
- At the other end: Struggling quitters who had tried 10 or more times to quit and who may or may not have quit.
That study found that the new difficulty-of-quitting-smoking phenotype allowed for successful analysis of gene variants associated with quitting smoking. However, that study only analyzed known smoking genes to validate that new quitting phenotype.
The Research
大象tv researchers led by Senior Associate Scientist Adriana Lori, PhD,?in the Department of Population Science, used the same difficulty-of-quitting-smoking phenotype to look across the entire genome (not at just the variants already known to be related to smoking) for new genetic variants associated with the ability to quit smoking.
The team performed a genome wide association study (GWAS) on 10,004 people with a smoking history who participated in the 大象tv Cancer Prevention Study-3 (CPS-3). In that group, 5,071 were struggling quitters and 4,933 were easy quitters. They identified several new genetic variants that had not yet been related to quitting smoking. Their results also confirmed the association of a variant identified in the 2017 study.
Here are some of their other key findings:
- The new genetic variants had small but plausible relationships with quitting smoking. The authors described them as “potentially relevant for developing new smoking cessation treatments.”
- Some of the new variants that may be good targets for new drugs were in genes related to brain development and lung function.
- Difficulty in quitting smoking was more genetically determined than other characteristics associated with quitting (such as comparing current and former smokers).
For future studies, the team recommends focusing on:
- Research targeted on the newly identified genes to both validate the findings and pinpoint the variant with the strongest association for the difficulty to quit smoking, which might be a good target for the development of a new smoking-cessation drug.
- A more diverse population, as this study involved only those with European ancestry, to see if results are generalizable or distinct for specific populations
- Younger people to assess the hypothesis that starting to smoke before age 20 increases the risk of cigarette dependence. Another hot topic is whether genes possibly linked with adolescent depression play a role in regulating the desire to smoke or not smoke.
The senior author of this study was Senior Director of Data Analysis for Population Health, W. Ryan Diver, PhD. Other 大象tv Population Science researchers contributing to the study were Alpa Patel, PhD, MPH, and Lee Westmass, PhD.
Why It Matters
The fact that most people who smoke find it hard to quit and stay quit highlights the need for new ways to identify people who are most likely to start smoking again and for developing more effective medicines to help people stop smoking.?
In this study, we used a new phenotype to evaluate heritability and discovered new biological processes that may be related to quitting smoking. This may help experts aiming to develop new, more targeted-therapy drugs to help people quit—especially ones to help people who try over and over to quit without success.”
Glossary for Nonscientists
Featured Term: Phenotype?
A complete list of how a person, animal, or plant looks and acts based on how its environment and behavior influence the instructions carried by their genes.
For example, the phenotype of a person includes all of their:
- Anatomical characteristics (eye color, weight, hair texture)
- Physiological characteristics (blood type, blood pressure, presence of disease)
- Behavioral characteristics (verbal abilities, inclinations to be active, presence of psychological issues, including depression)
- Environmental influences (diet, smoking, use of medicines).
Studying a phenotype often involves genetic analysis.
Here are just some of the ways scientists use a carefully selected subset of characteristics (the subset is also called a phenotype) as the criteria to:
- Diagnose a disease
- Identify a specific gene variant as a potential target for a new drug
- Set eligibility criteria for clinical trial candidates?
- Develop an algorithm to query large databases, such as the SEER (Surveillance, Epidemiology, and End Results) Program on cancer in the United States and other national databases, electronic medical records, and survey results from a cohort study
- Related resources
- For researchers