CYP1B1

Cytochrome P450 enzyme, family 1, subfamily B, polypeptide 1 (CYP1B1) is located on the

short arm of chromosome 2, at location 22-22 (Tang et al.,1996). CYP1B1 genes are not active

in the liver, but are found in the adrenal, ovary, testis (Tang et al., 1996), breast, uterine

(Nakajima & Yokoi, 2014), lung, colon, eye, and kidney (Li & Gonzales, 2017) tissues. CYP1B1

activity is induced by endogenous compounds such as estrogen, arachidonic acid, melatonin,

retinoids (Nakajima & Kokoi, 2014), adrenocorticotropin, and peptide hormones (Tang et al.,

1996), as well as by exogenous compounds such as xenoestrogens, planar aromatic hydrocarbons

(Tang et al., 1996). 

Upregulated CYP1B1 results in increased metabolism of procarcinogen activity and has been

observed in disease states such as polycystic ovary syndrome (Kokosar et al., 2016) and cancers

of the breasts (Almeida et al., 2021; Golmohammadzadeh et al., 2019; Kocabas et al., 2002;

Saini et al., 2009), prostate (Gu et al., 2018; Zhu et al., 2019), uterus (Sasaki et al., 2003), lung

(Gorain et al., 2019), and brain (Saini et al., 2009).

Certain single nucleotide polymorphisms (SNPs) have been identified as positively correlated to

the upregulation of CYP1B1. For example, rs1056836 (a.k.a. Val432Leu) is associated with

increased metabolism of procarcinogens as well as increased risk of PCG and POCS (Angel &

DiGiovanni, 2018; Elfaki et al., 2018; Chouiter & Nadifi, 2017; Kokosar et al., 2016). CYP1B1

rs1056836 CG and GG polymorphisms are associated with a lower risk of cancer while the

rs1056836 CC polymorphism is associated with an increased risk of cancer (Gu et al., 2018).
The by-product of estrogen metabolism by CYP1B1 is 4-hydroxyestradiol, a carcinogen (Gorain

et al., 2019; Nakajima & Yokoi, 2014). If CYP1B1 metabolizes excessive amounts of estrogen,

high levels of 4-hydroxyestradiol, reactive oxygen species, and DNA adducts will be the result;

this in turn increases the risk of certain cancers (Gu et al., 2018). Exposure to xenoestrogens in

the environment are also metabolized by CYP1B1 and thus increase production of 4-

hydroxyestradiol to potentially harmful levels (Gu et al., 2018). 

Truncations and mutations in the CYP1B1 gene resulting in primary congenital glaucoma (PCG)

have been found in certain populations (Alsubait et al., 2020; Wiggs, 2007), especially

consanguineous communities (Chouiter & Nadifi, 2017; Rashid et al., 2019). Upregulation of

CYP1B1 may also cause obesity while suppressing CYP1B1 increases fatty acid metabolism

(Liu et al., 2015). There also seems to be a positive correlation between pre-diabetes and

upregulation of CYP1B1 (Elfaki et al., 2018; Kokosar et al., 2016).

Dozens of loss of function mutations in CYP1B1 have been identified in familial groups and

communities where there is a high incidence of PCG (Rachid et al., 2019; Wiggs, 2015). These

mutations result in “missense, frameshift, premature stop codons, small insertion/deletions, and

large deletions” (Wiggs, 2015). 

Individuals with CYP1B1 rS1056836 benefit from down regulating activity of CYP1B1. The

most important step is to avoid all xenoestrogens, which are prolific in cleaning products and

personal care products (e.g. lotions, soaps, shampoos) which contain synthetic fragrances,

bisphenol A (BPA), phthalates, and parabens. Ginkgo biloba has been observed to upregulate

CYP1B1 activity and therefore should also be avoided by individuals with the rs1056836
polymorphism (Chang et al., 2006). These individuals must also avoid smoking tobacco (Port et

al., 2004)

Compounds that downregulate CYP1B1 activity include licorice (Glycyrrhiza glabra) (Dunlap et

al., 2015), resveratrol (Pervaiz & Holme, 2009), berberine (Lo et al., 2013), cannabinol

(Oultram,2021), and flavonoids, such as those that are found in hops, grapefruit, and quercetin

(Chang, 2006; Choi, 2012; Li et al., 2017). Foods and supplements containing the

aforementioned compounds will reduce the production of 4-hydroxyestradiol by inhibiting

CYP1B1 activity. 

On the other hand, foods and supplements that upregulate CYP1A1 may also have health

benefits. CYP1A1 is another Cytochrome P450 gene that metabolizes estrogen. The by-product

of estrogen metabolism by CYP1A1 is 2-hydroxyestradiol, which is associated with normal cell

differentiation and apoptosis (Samavat & Kurzer, 2015); these are foods such as cruciferous

vegetables (Little et al.,2006) and berries (Ayer, 2010). 

Ensuring adequate catechol-O-methyltransferase (COMT) activity may offer protection against

cancer as it is responsible in the last step of removing 2-hydroxyestradiol and 4-hydroxyestradiol

carcinogenic estrogen metabolites (Zahid et al.,2007). However, abnormally-high COMT

activity depletes catecholamines and may have detrimental effects on cognitive function (e.g.

schizophrenia, depression) (Simpson et al., 2014).

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