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CYP2A6 Enzyme: The Link Between Nicotine & Genetics

Written by Biljana Novkovic, PhD | Last updated:

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.

What is CYP2A6?

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 [1].

Read more about CYPs here.

CYP2A6 Function

This enzyme metabolizes:

  • Nicotine, the main active component in cigarette smoke [2]. About 90% of nicotine is processed by this enzyme [3].
  • Hormones and internal molecules, such as retinoic acid, testosterone, estradiol, and progesterone. But the contribution of CYP2A6 activity is minor in their overall pathways [4].
  • Coumarin [4, 5], found in plants.
  • Nitrosamines and aflatoxin B1 [6].
  • Letrozole, an aromatase inhibitor used to treat breast cancer [7].

CYP2A6 Location

This enzyme is mainly found in the liver. It accounts for about 10% of the total liver CYP enzyme content [4].

At much lower levels, it can be found in some other tissues, especially the mucous lining of the nose [4].

Some people completely lack the functional CYP2A6 gene and enzyme [4].

CYP2A6 The Bad

There is a clear link between CYP2A6 enzyme activity, smoking behavior, and lung cancer risk [4].

This enzyme can activate several cancer-causing agents found in tobacco smoke and diet, such as nitrosamines (e.g. NNK) and aflatoxins [5].

Several studies show that gene variants that decrease this enzyme’s activity also decrease the risk of lung cancer [8].

The activity of this enzyme can contribute to liver damage. A study showed that being a CYP2A6 poor metabolizer type (having lower enzyme activity) protects against liver cirrhosis [5].

CYP2A6 Gene Polymorphism

This gene has around 40 variants [4].

The activity of this enzyme can vary up to 12-fold, based on the particular gene variant [7].

Slow CYP2A6 metabolism (low activity) is associated with lower cigarette consumption, lower dependence, and higher cessation rates in adults (421 subjects) [9].

However, slow metabolism was also associated with more cigarettes smoked per day and a greater dependence in adolescents (296 smokers) [10, 9].

Some people completely lack this gene [4]. They are labeled as CYP2A6*4.

CYP2A6*4 is associated with a lower risk of lung cancer (242 subjects) [11].

  • RS1801272

rs1801272 A is associated with a decreased lung cancer risk (squamous cell carcinoma) (4221 subjects) [6].

This variant is also associated with lower cigarette dependence (4221 subjects) [6].

Increasing or Decreasing CYP2A6

These substances increase CYP2A6:

  • Antiepileptic drugs phenytoin, phenobarbital, and carbamazepine [4].
  • The antibiotic rifampicin [4].

These decrease CYP2A6:

  • Smoking [4] – due to an unknown compound in cigarettes other than nicotine.
  • Starfruit juice [12].
  • Cinnamaldehyde found in cinnamon [7].
  • Celery [13].
  • Drugs such as methoxsalen, menthofuran, pilocarpine, and tranylcypromine [5].
  • Isoniazid, an antibacterial [14].

About the Author

Biljana Novkovic

Biljana Novkovic

Biljana received her PhD from Hokkaido University.
Before joining SelfHacked, she was a research scientist with extensive field and laboratory experience. She spent 4 years reviewing the scientific literature on supplements, lab tests and other areas of health sciences. She is passionate about releasing the most accurate science and health information available on topics, and she's meticulous when writing and reviewing articles to make sure the science is sound. She believes that SelfHacked has the best science that is also layperson-friendly on the web.


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