What you carry at this position in your DNA and what research says about it.
Nicotine Metabolism: 8/10 evidence, 41 publications.
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Sample genotype (not yours): T/T
Slower Nicotine Metabolism and Lower Lung Cancer Risk
Slower clearance of nicotine helps reduce the urge to smoke frequently. This natural pacing significantly lowers the risk of developing lung cancer and makes quitting smoking easier.
What this genotype means: Slower clearance of nicotine; Lower risk of lung cancer; Fewer cigarettes smoked per day.
Sample genotype (not yours): C/C
Faster Nicotine Metabolism and Higher Lung Cancer Risk
Rapid clearance of nicotine drives more frequent smoking to maintain active levels. This increased consumption, combined with faster carcinogen activation, raises lung cancer risk.
What this genotype means: Rapid clearance of nicotine; Higher risk of lung cancer; More cigarettes smoked per day.
Sample genotype (not yours): T/C
Typical Nicotine Metabolism and Average Lung Cancer Risk
An intermediate rate of nicotine clearance results in typical smoking behaviors. Lung cancer risk and smoking cessation success rates remain close to the population average.
What this genotype means: Typical nicotine clearance rate; Average risk of lung cancer; Standard caffeine clearance.
Gene function and biological role
Gene Function: The CYP2A6 gene encodes a major liver enzyme responsible for metabolizing nicotine and several clinical drugs [1]. This enzyme inactivates nicotine by converting it into cotinine, which is then further metabolized into 3-hydroxycotinine [1]. Genetic variation in this gene is a primary driver of how quickly or slowly an individual clears nicotine from their bloodstream [1]. Beyond nicotine, the enzyme is also involved in activating pre-carcinogens found in tobacco smoke into active cancer-causing agents [2]. Consequently, differences in CYP2A6 activity heavily influence smoking behaviors, tobacco dependence, and the risk of tobacco-related cancers [2].
Variant Impact: This intronic variant alters the expression level of the CYP2A6 enzyme, directly impacting its metabolic rate. The C allele is associated with increased enzyme expression and significantly faster nicotine clearance [3]. Conversely, the T allele reduces enzyme activity, leading to slower nicotine breakdown [3]. Because nicotine clearance rates dictate smoking frequency and carcinogen exposure, this genetic change is a major predictor of lung cancer susceptibility [4]. It also influences how individuals respond to smoking cessation therapies and clear other dietary substances like caffeine.
Key Insight: Slower nicotine metabolizers naturally smoke fewer cigarettes because nicotine stays in their system longer, which unexpectedly lowers their lung cancer risk.
Location: CYP2A6. Chromosome 19 · 19q13.2 · 40.8 Mb
Estimated prevalence by population
Global 24.1%; European 17.5%; African 35.7%; East Asian 45.6%; South Asian 34.4%; Americas 17.3%; Ashkenazi 18.1%; Finnish 18.7%; Middle Eastern 19.3%; Amish 9.9%.
Estimated TT genotype frequency.
Global 48.3%; European 48.7%; African 48.1%; East Asian 43.9%; South Asian 48.5%; Americas 48.6%; Ashkenazi 48.9%; Finnish 49.1%; Middle Eastern 49.3%; Amish 43.1%.
Estimated TC genotype frequency.
Global 27.6%; European 33.8%; African 16.2%; East Asian 10.6%; South Asian 17.1%; Americas 34.1%; Ashkenazi 33.0%; Finnish 32.3%; Middle Eastern 31.5%; Amish 47.1%.
Estimated CC genotype frequency.
Showing effects for T/T genotype
Cancer & Oncology
Lung Cancer
Lung Cancer. Evidence: 8/10. Source: PMID 28604730. Lower Risk.
Pharmacogenomics
Drug Metabolism Enzyme Activity
Nicotine Metabolism. Evidence: 8/10. Source: PMID 26407342. Slower Clearance.
Neurology & Mental Health
Addiction & Reward
Cigarettes Per Day. Evidence: 10/10. Source: PMID 30643251. Fewer Cigarettes.
Cardiovascular & Metabolic
Lipids & Cholesterol
LDL Cholesterol. Evidence: 8/10. Source: PMID 32203549. Lower Levels.
Nutrition & Metabolism
Caffeine & Stimulant Metabolism
Caffeine Metabolism. Evidence: 8/10. Source: PMID 40962832. Slower Clearance.
Showing effects for C/C genotype
Lung Cancer. Evidence: 8/10. Source: PMID 28604730. ~1.1x Higher Risk.
Nicotine Metabolism. Evidence: 8/10. Source: PMID 26407342. Faster Clearance.
Cigarettes Per Day. Evidence: 10/10. Source: PMID 30643251. More Cigarettes.
LDL Cholesterol. Evidence: 8/10. Source: PMID 32203549. Higher Levels.
Caffeine Metabolism. Evidence: 8/10. Source: PMID 40962832. Faster Clearance.
Showing effects for T/C genotype
Lung Cancer. Evidence: 8/10. Source: PMID 28604730. Typical Risk.
Nicotine Metabolism. Evidence: 8/10. Source: PMID 26407342. Typical Clearance.
Cigarettes Per Day. Evidence: 10/10. Source: PMID 30643251. Typical.
LDL Cholesterol. Evidence: 8/10. Source: PMID 32203549. Typical Levels.
Caffeine Metabolism. Evidence: 8/10. Source: PMID 40962832. Slightly Faster.
What this genotype means for the people who carry it
Sample genotype: TT (Homozygous)
Slower breakdown of nicotine occurs in the liver due to reduced enzyme activity associated with this genotype [1]. Because nicotine remains in the bloodstream for an extended duration, the biological drive to smoke another cigarette is naturally delayed [2]. Research shows that smokers with this genotype consume fewer cigarettes per day and find smoking cessation more achievable [3]. Furthermore, a lower rate of nicotine metabolism reduces the activation of harmful tobacco-specific procarcinogens [2]. This combined effect results in a significantly lower risk of developing lung cancer, including squamous cell carcinoma [2]. Non-smokers with this genotype do not experience these specific tobacco-related risks or protective benefits. Additionally, this genotype is associated with slightly lower LDL cholesterol levels and slower clearance of caffeine.
Slower clearance of nicotine; Lower risk of lung cancer; Fewer cigarettes smoked per day; Easier smoking cessation.
Sample genotype: CC (Homozygous)
Rapid clearance of nicotine from the bloodstream is driven by highly active liver enzymes in this genotype [1]. Because nicotine is broken down quickly, smokers feel the urge to light up more frequently to maintain stable nicotine levels in the brain [1]. This rapid metabolism is strongly linked to smoking more cigarettes per day and experiencing greater difficulty when trying to quit [1]. Crucially, the same enzyme bioactivates tobacco-specific nitrosamines into potent carcinogens [2]. The combination of higher tobacco exposure and increased carcinogen activation leads to a significantly higher risk of lung cancer, particularly squamous cell lung cancer [2]. For non-smokers, this genotype does not elevate lung cancer risk but is associated with slightly higher LDL cholesterol levels [3]. Additionally, caffeine is cleared more rapidly, which may increase daily coffee consumption.
Rapid clearance of nicotine; Higher risk of lung cancer; More cigarettes smoked per day; Harder to quit smoking.
Sample genotype: TC (Heterozygous)
An intermediate rate of nicotine clearance is typical for this genotype, balancing fast and slow metabolic pathways [1]. The presence of one copy of each allele results in moderate enzyme activity in the liver [1]. Smoking behaviors, such as the average number of cigarettes consumed daily, generally align with population baselines [1]. Similarly, the risk of developing lung cancer or other tobacco-related diseases is not significantly elevated or reduced compared to the average smoker [1]. When attempting to quit smoking, standard cessation strategies typically show average rates of success. This genotype also exhibits typical levels of LDL cholesterol and average kidney filtration rates. Interestingly, some studies suggest a slightly faster metabolism of caffeine compared to those with two copies of the slower-metabolizing allele [2].
Typical nicotine clearance rate; Average risk of lung cancer; Standard caffeine clearance.
Variants with shared genetic architecture
rs28399433 · CYP2A6 Gene · Chr 19 · Nicotine and Drug Metabolism
rs1801272 · CYP2A6 Gene · Chr 19 · Nicotine Metabolism
rs28399454 · CYP2A6 Gene · Chr 19 · Nicotine Metabolism
A Genome-Wide Association Study of a Biomarker of Nicotine Metabolism.
Genome-Wide Association of the Laboratory-Based Nicotine Metabolite Ratio in Three Ancestries.
Content updated August 2026.
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