What you carry at this position in your DNA and what research says about it.
Nicotine Metabolism: 3/10 evidence, 1 publications.
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Sample genotype (not yours): C/C
Typical Nicotine Metabolism and Average Lung Cancer Risk
Normal enzyme activity leads to typical nicotine clearance rates. This results in standard smoking patterns and average susceptibility to tobacco-related health risks.
What this genotype means: Typical nicotine clearance rate; Standard smoking frequency; Baseline lung cancer risk if a smoker.
Sample genotype (not yours): C/T
Slower Nicotine Metabolism and Lower Lung Cancer Risk
Reduced enzyme activity slows down the clearance of nicotine from the body. This often leads to smoking fewer cigarettes and a decreased risk of tobacco-related cancers.
What this genotype means: Slower nicotine clearance; Reduced cigarette consumption; Lower lung cancer risk if a smoker.
Sample genotype (not yours): T/T
Slowest Nicotine Metabolism and Lowest Lung Cancer Risk
Highly reduced enzyme activity causes nicotine to clear very slowly. This is linked to significantly lower cigarette consumption and the lowest risk of tobacco-related cancers.
What this genotype means: Very slow nicotine clearance; Significantly reduced cigarette consumption; Lowest lung cancer risk if a smoker.
Gene function and biological role
Gene Function: Cytochrome P450 2A6, encoded by the CYP2A6 gene, is the primary enzyme responsible for metabolizing nicotine in the human body. It converts nicotine into cotinine, which is further processed before excretion. This enzyme also plays a critical role in activating several pre-carcinogens found in tobacco smoke, such as nitrosamines. Genetic variations that alter the activity of this enzyme can significantly influence smoking behavior, nicotine dependence, and tobacco-related health risks.
Variant Impact: The rs28399454 variant is a missense mutation in the CYP2A6 gene, resulting in a valine to methionine substitution at position 365. This specific change defines the CYP2A6*17 allele, which is highly prevalent in populations of African ancestry. The substitution alters the enzyme's structure, leading to significantly reduced expression and stability. Consequently, individuals carrying this variant experience a marked decrease in their ability to metabolize nicotine and certain medications.
Key Insight: Slower nicotine metabolizers tend to smoke fewer cigarettes per day because nicotine remains in their system longer. This genetic variant is primarily found in people of African ancestry and is virtually absent in European and East Asian populations.
Location: CYP2A6. Chromosome 19 · 19q13.2 · 40.8 Mb
Estimated prevalence by population
Global 94.3%; European 99.9%; African 80.4%; East Asian 100.0%; South Asian > 99.9%; Americas 97.7%; Ashkenazi 100.0%; Finnish 100.0%; Middle Eastern 98.0%; Amish 100.0%.
Estimated CC genotype frequency.
Global 5.4%; European 0.1%; African 18.5%; East Asian 0.0%; South Asian < 0.1%; Americas 2.3%; Ashkenazi 0.0%; Finnish 0.0%; Middle Eastern 2.0%; Amish 0.0%.
Estimated CT genotype frequency.
Global 0.3%; European < 0.1%; African 1.1%; East Asian 0.0%; South Asian < 0.1%; Americas < 0.1%; Ashkenazi 0.0%; Finnish 0.0%; Middle Eastern < 0.1%; Amish 0.0%.
Estimated TT genotype frequency.
Showing effects for C/C genotype
Cancer & Oncology
Lung Cancer
Lung Cancer. Evidence: 3/10. Source: PMID 40829600. Typical Risk.
Pharmacogenomics
Drug Metabolism Enzyme Activity
Nicotine Metabolism. Evidence: 3/10. Typical.
Antimicrobial & Antiviral Response
Efavirenz Sensitivity. Evidence: 3/10. Typical.
Neurology & Mental Health
Addiction & Reward
Cigarettes Per Day. Evidence: 3/10. Typical.
Showing effects for C/T genotype
Lung Cancer. Evidence: 3/10. Source: PMID 40829600. Lower Risk.
Nicotine Metabolism. Evidence: 3/10. Slower.
Efavirenz Sensitivity. Evidence: 3/10. Increased.
Cigarettes Per Day. Evidence: 3/10. Reduced.
Showing effects for T/T genotype
Lung Cancer. Evidence: 3/10. Source: PMID 40829600. Lowest Risk.
Nicotine Metabolism. Evidence: 3/10. Slowest.
Efavirenz Sensitivity. Evidence: 3/10. Highly Increased.
Cigarettes Per Day. Evidence: 3/10. Significantly Reduced.
What this genotype means for the people who carry it
Sample genotype: CC (Homozygous)
Normal functioning of the CYP2A6 enzyme ensures that nicotine is cleared from the bloodstream at a standard rate. Because nicotine is processed quickly, individuals who smoke may feel the urge to light up more frequently to maintain stable nicotine levels. This rapid metabolism is also associated with a higher rate of converting tobacco-specific nitrosamines into active carcinogens. Consequently, smokers with this genotype face a typical, unmodified risk of developing lung cancer [1]. This genotype represents the most common genetic baseline globally.
Typical nicotine clearance rate; Standard smoking frequency; Baseline lung cancer risk if a smoker.
Sample genotype: CT (Heterozygous)
Carrying one copy of the reduced-function T allele (CYP2A6*17) decreases the overall activity of the nicotine-metabolizing enzyme. Because nicotine remains in the circulation for a longer duration, individuals who smoke generally require fewer cigarettes to satisfy their cravings. This slower processing also reduces the rate at which tobacco-smoke toxins are activated into harmful carcinogens in the body. As a result, smokers with this genotype have a significantly lower risk of developing lung cancer compared to typical metabolizers [1]. Additionally, this genotype can lead to higher blood levels of certain medications, such as the HIV drug efavirenz, which are processed by the same pathway.
Slower nicotine clearance; Reduced cigarette consumption; Lower lung cancer risk if a smoker.
Sample genotype: TT (Homozygous)
Having two copies of the T allele results in a profound reduction in CYP2A6 enzyme function. Nicotine is metabolized at an exceptionally slow rate, meaning very small amounts of nicotine can persist in the body for extended periods. For smokers, this dramatic reduction in clearance typically translates to a much lower daily cigarette consumption and a higher likelihood of successfully quitting. Furthermore, the body's activation of tobacco-smoke carcinogens is minimized, leading to the lowest relative risk of lung cancer among smokers [1]. This genotype also significantly slows the clearance of medications like efavirenz, potentially increasing the risk of drug-related side effects.
Very slow nicotine clearance; Significantly reduced cigarette consumption; Lowest lung cancer risk if a smoker.
Variants with shared genetic architecture
rs56113850 · CYP2A6 Gene · Chr 19 · Nicotine Metabolism
rs28399433 · CYP2A6 Gene · Chr 19 · Nicotine and Drug Metabolism
rs1801272 · CYP2A6 Gene · Chr 19 · Nicotine Metabolism
Content updated August 2026.
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