CYP1A1: Detoxifying Cigarette Smoke and Estrogen

CYP1A1 is a gene that codes for an enzyme that breaks down (metabolizes) a few different toxins as well as naturally produced hormones. It is also involved in immune response in the intestines.

This article explains how CYP1A1 works, how genetic variants impact your detoxification of certain substances, and how to mitigate the negative impacts. Members will see their genotype report below, plus additional solutions in the Lifehacks section. Join today 

CYP1A1 and Metabolism of Estrogen, Cigarette Smoke, and More

Genetic variants in the CYP1A1 gene are linked to a number of different health conditions, including an increased risk for estrogen-related cancers and an increased risk for lung cancer in smokers.

A quick overview of phase I detoxification :

Everything you eat or take (like a medication) is absorbed in the intestines and taken to the liver.

  • This allows the liver to detoxify anything harmful that you’ve eaten and it also transforms nutrients into forms that you need.
  • Fat-soluble toxins are made water-soluble.
  • Then the toxin can be transformed and eliminated (mainly through the kidneys).

Related article: Overview of Phase I and Phase II detoxification

CYP1A1: What does it do?

The CYP450 (cytochrome P450) family of enzymes metabolize or break down thousands of different compounds. CYP1A1 is one member of the CYP family of enzymes which are involved in metabolizing lots of different toxins as well as substances the body makes.

  • The CYP1A1 enzyme involved in the metabolism of poly-aromatic hydrocarbons (PAH) in the intestines, thus playing a role in smoking-related cancers from the activation of the aromatic hydrocarbons. In addition to cigarette smoke, aromatic hydrocarbons are also found in wood smoke, vehicle exhausts, asphalt, and charred meats.
  • CYP1A1 is also involved in the metabolism of estrogen – specifically 17β-estradiol – as well as arachidonic acid and DHA (fatty acids).
  • New research points to a role in immune homeostasis in the intestines.[ref]
  • A study on workers in China showed that those with CYP1A1 variants had lower acetylcholinesterase levels due to glyphosate (RoundUp ingredient) exposure. Lower acetylcholinesterase was assumed to be a marker of liver damage.[ref]

Fast and slow CYP1A1 metabolism:

There are several genetic variants of CYP1A1 that can change the speed at which your body will metabolize substances.

  • Increased CYP1A1 metabolism can cause the buildup of the intermediate metabolites if your body can’t get rid of them fast enough through phase II metabolism.
  • Increased CYP1A1 activity can also increase the degradation of the aryl hydrocarbon receptor, which is an important mechanism for binding poly-aromatic hydrocarbons.[ref]

CYP1A1 Genotype Report

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CYP1A1*2:  increased enzyme activity

Check your genetic data for rs1048943 A2455G (23andMe v.4 only)

  • T/T: typical
  • C/T:  carrier of one CYP1A1*2 allele; smokers have a higher risk of lung cancers; higher activity in estrogen metabolism
  • C/C: CYP1A1*2; higher risk of oral cancer & lung cancers in smokers; higher activity in estrogen metabolism[ref][ref][ref]

Members: Your genotype for rs1048943 is .

Studies on CYP1A1*2 show a link to estrogen-related cancers, but the results vary according to population and possibly diet:

  • A study in China showed that the CYP1A1*2 polymorphism had a lower risk of breast cancer.[ref]
  •  Another study showed that those with CYP1A1*2 had more inhibition with natural polyphenols (high fruit and vegetable diet) than those without the polymorphism.[ref]
  • A study showed that CYP1A1*2 has a significantly higher activity level of estrogen metabolism which “may either increase or reduce the susceptibility to cancer depending on its combination with other genetic and environmental risk factors…“[ref]

CYP1A1*4 allele:

The CYP1A1*4 variant has somewhat increased enzyme activity.

Check your genetic data for rs1799814  A2452C (23andMe v.4, v.5; AncestryDNA):

  • G/G: typical
  • G/T: one CYP1A1*4 allele
  • T/T: increased enzyme activity, CYP1A1*4[ref]

Members: Your genotype for rs1799814 is .

Studies on CYP1A1*4 show it to be protective against certain cancers, and others show it to slightly increase risk depending on the population and diet.[ref][ref][ref]  Some studies show that the CYP1A1*4 allele is protective against lung cancer.[ref] A meta-analysis found it to be a risk factor for thyroid cancer.[ref]

Other CYP1A1 alleles:

While the two variants above seem to have the most impact, there are a few other CYP1A1 variants that have been studied for various health effects.

Check your genetic data for rs2606345 (23andMe v4, v5; AncestryDNA):

  • C/C typical
  • A/C: decreased risk of testicular cancer, decreased risk of pneumonia
  • A/A: decreased risk of testicular cancer[ref] decreased risk of pneumonia[ref]

Members: Your genotype for rs2606345 is .

Check your genetic data for rs2472297 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: associated with slightly increased coffee consumption
  • T/T: associated with increased coffee consumption[ref]

Members: Your genotype for rs2472297 is .

 


Lifehacks:

Higher CYP1A1 activity is going to be detrimental when exposed to PAHs (such as in cigarette smoke and smog). But, higher CYP1A1 activity is going to break down estrodiol faster, which may be beneficial in estrogen metabolism, depending on your other estrogen-related genes.

Stop smoking:
People with the CYP1A1*2 allele are at a higher risk for lung cancer and definitely should avoid cigarette smoke. So if you need yet another reason to stop smoking, this would be a big one.

Eat your veggies:
One study found that people who carried the CYP1A1*2  variant had a greater reduction in colon cancer risk with a diet high in polyphenols (found in veggies and fruit) than those without the variant.[ref]

Grapefruit juice also inhibits CYP1A1.[ref]


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Supplements and CYP1A1:

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Related Genes and Topics:

CYP2C9: 
Have you ever wondered why certain medications don’t work well for you? Genetic variants can change how fast or how slow the medication is broken down in your body.

CYP2D6: Reactions to Common Medications
The CYP2D6 enzyme is involved in the metabolism of about 25% of medicaitons.

 

 


About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering and also an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.