CYP2A6 is the detox enzyme responsible for eliminating nicotine. There is a link between this enzyme’s activity, smoking, and lung cancer risk. Read on to find more about this enzyme, how having a particular gene variant may affect you, and the factors that increase or decrease its activity.



CYP2A6 enzyme is one of the cytochrome P450 monooxygenases (CYPs). These are enzymes that eliminate most of the drugs and toxins from the human body (R).

Read more about CYPs here.

CYP2A6 Function

This enzyme metabolizes:

  • Nicotine, the main active component in cigarette smoke (R). About 90% of nicotine is processed by this enzyme (R).
  • Hormones and internal molecules, such as retinoic acid, testosterone, estradiol, and progesterone. But the contribution of CYP2A6 activity is minor in their overall pathways (R).
  • Coumarin (R, R), found in plants.
  • Nitrosamines and aflatoxin B1 (R).
  • Letrozole, an aromatase inhibitor used to treat breast cancer (R).

CYP2A6 Location

This enzyme is mainly found in the liver. It accounts for about 10% of the total liver CYP enzyme content (R).

At much lower levels, it can be found in some other tissues, especially the mucous lining of the nose (R).

Some people completely lack the functional CYP2A6 gene and enzyme (R).

CYP2A6 The Bad

There is a clear link between CYP2A6 enzyme activity, smoking behavior, and lung cancer risk (R).

This enzyme can activate several cancer-causing agents found in tobacco smoke and diet, such as nitrosamines (e.g. NNK) and aflatoxins (R).

Several studies show that gene variants that decrease this enzyme’s activity also decrease the risk of lung cancer (R).

The activity of this enzyme can contribute to liver damage. A study showed being a CYP2A6 poor metabolizer type (having lower enzyme activity) protects against liver cirrhosis (R).

CYP2A6 Gene Polymorphism

This gene has around 40 variants (R).

The activity of this enzyme can vary up to 12-fold, based on the particular gene variant (R).

Slow CYP2A6 metabolism (low activity) is associated with lower cigarette consumption, lower dependence, and higher cessation rates in adults (421 subjects) (R).

However, slow metabolism was also associated with more cigarettes smoked per day and a greater dependence in adolescents (296 smokers) (R, R).

Some people completely lack the this gene (R). They are labeled as CYP2A6*4.

CYP2A6*4 is associated with a lower risk of lung cancer (242 subjects) (R).

rs1801272 A is associated with a decreased lung cancer risk (squamous cell carcinoma) (4221 subcjects) (R).

This variant is also associated with lower cigarette dependence (4221 subjects) (R).

Increasing or Decreasing CYP2A6

These substances increase CYP2A6:

These decrease CYP2A6:

Health Tools I Wish I Had When I Was Sick

At SelfHacked, it’s our goal to offer our readers all the tools possible to get optimally healthy. When I was struggling with chronic health issues I felt stuck because I didn’t have any tools to help me get better. I had to spend literally thousands of hours trying to read through studies on pubmed to figure out how the body worked and how to fix it.

That’s why I decided to create tools that will help others cut down the guesswork:

  • Lab Test Analyzer – a software tool that will analyze your labs and tell you what the optimal values are for each marker — as well as provide you with actionable tips and personalized health and lifestyle recommendations to help you get there.
  • SelfDecode – a software tool that will help you analyze your genetic data from companies such as 23andme and ancestry. You will learn how your health is being impacted by your genes, and how to use this knowledge to your advantage.
  • SelfHacked Secrets – an ebook where we examine and explain the biggest overlooked environmental factors that cause disease. This ebook is a great place to start your journey if you want to learn the essential steps to optimizing your health.
  • SelfHacked Elimination Diet course – a video course that will help you figure out which diet works best for you
  • Selfhacked Inflammation course – a video course on inflammation and how to bring it down
  • Biohacking insomnia – an ebook on how to get great sleep
  • Lectin Avoidance Cookbook – an e-cookbook for people with food sensitivities
  • BrainGauge – a device that detects subtle brain changes and allows you to test what’s working for you
  • SelfHacked VIP – an area where you can ask me (Joe) questions about health topics

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.


1 Star2 Stars3 Stars4 Stars5 Stars (No Ratings Yet)

Why did you dislike this article?