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 .
This enzyme metabolizes:
- Nicotine, the main active component in cigarette smoke . About 90% of nicotine is processed by this enzyme .
- Hormones and internal molecules, such as retinoic acid, testosterone, estradiol, and progesterone. But the contribution of CYP2A6 activity is minor in their overall pathways .
- Coumarin [4, 5], found in plants.
- Nitrosamines and aflatoxin B1 .
- Letrozole, an aromatase inhibitor used to treat breast cancer .
This enzyme is mainly found in the liver. It accounts for about 10% of the total liver CYP enzyme content .
At much lower levels, it can be found in some other tissues, especially the mucous lining of the nose .
Some people completely lack the functional CYP2A6 gene and enzyme .
CYP2A6 The Bad
There is a clear link between CYP2A6 enzyme activity, smoking behavior, and lung cancer risk .
This enzyme can activate several cancer-causing agents found in tobacco smoke and diet, such as nitrosamines (e.g. NNK) and aflatoxins .
Several studies show that gene variants that decrease this enzyme’s activity also decrease the risk of lung cancer .
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 .
CYP2A6 Gene Polymorphism
This gene has around 40 variants .
The activity of this enzyme can vary up to 12-fold, based on the particular gene variant .
Slow CYP2A6 metabolism (low activity) is associated with lower cigarette consumption, lower dependence, and higher cessation rates in adults (421 subjects) .
Some people completely lack this gene . They are labeled as CYP2A6*4.
CYP2A6*4 is associated with a lower risk of lung cancer (242 subjects) .
This variant is also associated with lower cigarette dependence (4221 subjects) .