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.

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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 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).

CYP1A1 gene:

The CYP450 (cytochrome P450) family of enzymes metabolize or break down thousand of different compounds. CYP1A1 is one member of the CYP family.

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. Aromatic hydrocarbons are also found in wood smoke, vehicle exhausts, asphalt, and charred meats.
In addition to toxins we may breathe in or eat, 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]

CYP1A1 is an NADPH dependent enzyme. Breaks down caffeine, theobromine,

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 Genetic Variants:

Members: See your data below

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 have 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 a 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:

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.

Supplements:
CYP1A1 is inhibited by several natural polyphenols including St. John’s Wort, I3C, and resveratrol.[ref] Foods containing I3C include broccoli and other cruciferous vegetables. Resveratrol is found in grapes and red wine as well as in supplement form.

Inhibiting CYP1A1 may help increase the aryl hydrocarbon receptors, which bind to PAHs and theoretically could decrease cancer risk.[ref]

Camel milk inhibits CYP1A1.
Interestingly, camel milk has traditionally been thought to be protective against cancer in the Middle East. Researchers found that smokers with CYP1A1*2 variants who drink camel milk reduce the high risk of lung cancer.[ref]

Eat your veggies:
One study found that people who carry 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]