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CYP1A1

Cytochrome P-450 1A1

Overview

CYP1A1 - also known as AHH [aryl hydrocarbon hydroxylase]

Is a protein member [enzyme] of the cytochrome P450 superfamily of enzymes. It is encoded by the CYP1A1 gene.

Single Nucleotide Polymorphisms Identified

Several polymorphisms have been identified in CYP1A1, some of which lead to more highly inducible AHH activity. CYP1A1 polymorphisms include:

  • M1, T→C substitution at nucleotide 3801 in the 3'-non-coding region
  • M2, A→G substitution at nucleotide 2455 leading to an amino acid change of isoleucine to valine at codon 462
  • M3, T→C substitution at nucleotide 3205 in the 3'-non-coding region
  • M4, C→A substitution at nucleotide 2453 leading to an amino acid change of threonine to asparagine at codon 461

The importance of CYP1A1

A double-edged sword

Why are CYP1A1 SNPs  important?

  • CYP1A1 is involved in phase-1 biotransformations of xenobiotics and drugs.
  • The biotransformations of chemicals either drugs or xenobiotics [toxic substances] by CYP1A1 can lead to either activation or inactivation of that chemical.
  • CYP1A1 can convert aromatic hydrocarbons (polycyclic aromatic hydrocarbons, PAH) and heterocyclic amines (HCA) ( which are toxic substances present in tobacco smoke and from high temperature cooking of meats) to carcinogens [cancer forming agents].
  • CYP1A1 can also have a beneficial effect if PAH and HCA are not competing for this enzyme in that it can convert dangerous estrogens to weaker ones and can thus decrease the risk of breast cancer.
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Understanding SNPs

What is an allele?

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  • Humans have paired homologous chromosomes in their cells [one from each parent]
  • The genotype for that gene is the set of alleles it happens to possess [one allele from each parent]
  • If one of the alleles has the C677T variant of the MTHFR gene example above then the individual is said to be heterozygous for this SNP variant
  • If both of the alleles has the C677T variants of the MTHFR gene then the individual is said to be homozygous for this SNP variant

Single Nucleotide Polymorphisms [SNPs]

Substitution of one nucleotide

Estrogen Metabolism

The role of CYP1A1, CYP1B1

Possible Dietary modification

CYP1A1

Diet

Whether a SNP produces an advantageous or deleterious effect will depend on the circumstance of the individual. A smoker or someone who consumes charred meat regularly [BBQ or flame heated meat] or those exposed to xenobiotics from the environment [pesticides, industrial chemicals] have the potential to bioconvert these hazardous compounds to even more carcinogenic substances.

However, if your gene profile shows a SNP with increased CYP1A1 activity then this can be favourable if an individual can avoid smoking and xenobiotics as much as possible and consumes a diet high in glucosinolate compounds that can further enhance the effect of CYP1A1 SNPs. 

Increasing 2 hydroxy estrogens will be of benefit to both the breast and prostate.

The Breast Health Diet provides you will detailed information dietary guidelines to provide a rich glucosinolate intake to shift CYP1A1 activity towards the production of beneficial metabolites.


Estrogen Metabolites

Measure Estrogen Metabolites 2OHE1 &16αOHE1

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What tests should be considered?

  • In women susceptible to breast disease or men with a risk of prostate cancer, assessing which type of estrogen [estradiol] breakdown product predominates is important. One of these called 2-hydroxyoestrone [2OHE1] is protective, the other 16α-hydroxyoestrone [16αOHE1] is highly estrogenic and a potent stimulator of estrogen-sensitive breast cancer cells in culture [Higdon 2007].
  • A urine test is available to identify which is the dominant pathway involved in you - 2OHE1 or 16αOHE1 for oestrogen metabolism.
  • The aim is to ensure that the ratio between the 2:16 pathways is maintained at the ideal of 2.0. Can you change this ratio? The aim of the diet is to change this ratio through wholefoods rich in glucosinolates and wholefood concentrates rich in cruciferous vegatables and to ensure the many other risk factors for breast cancer are minimized.

ARL Pathology - click on the link on the right. If you have a chronic illness or if you are feeling constantly unwell, especially so if you have an inflammatory disease such as arthritis, heart disease, diabetes or asthma and chronic lung disease. Checking essential fatty acid status may just be that important step you need towards good health. Testing takes the guesswork in terms of your dietary needs or supplementation.

References:

  • Muti et al 2000
  • Rees et al  2006.
  • Schneider et al 1984;

References

Nutrigenomics Section

  • Harris JI, Hibbeln JR, Mackey RH, Muldoon MF, Statin treatment alters serum n-3 and n-6 fatty acids in hypercholesterolemic patients. Prostaglandins, Leukotrienes and Essential Fatty Acids Volume 71, Issue 4, October 2004, Pages 263-269.
  • Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357:266-281.
  • Muti P, Bradlow HL, Micheli A, et al. Estrogen metabolism and risk of breast cancer: a
    prospective study of the 2:16alphahydroxyestrone ratio in premenopausal and
    postmenopausal women. Epidemiology 2000;11:635-640.
  • Norman AW. Minireview: vitamin D receptor: new assignments for an already busy receptor. Endocrinology
  • 2006;147:5542-5548.
  • Ortlepp JR, Metrikat J, Albrecht M et al. The vitamin D receptor gene variant and physical activity predicts fasting glucose levels in healthy young men. Diabet Med. 2003;20:451-454.
  • Rees D, Miles EA, Banerjee T, Wells SJ, Roynette CE, et al., Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. AM J Clin Nutr, 83:331 42, 2006.
  • Reis AF, Hauache OM, Velho G. Vitamin D endocrine system and the genetic susceptibility to diabetes, obesity, and vascular disease. A review of evidence. Diabetes Metab. 2005;31:318-325.
  • Schneider J, Huh MM, Bradlow HL, Fishman J. Antiestrogen action of 2-hydroxyestrone on MCF-7 human breast cancer cells. J Biol
    Chem 1984;259:4840-4845.
  • Taverna MJ, Selam JL, Slama G. Association between a protein polymorphism in the start codon of the vitamin D receptor gene and severe diabetic retinopathy in C-peptide-negative type 1 diabetes. J Clin Endocrinol Metab. 2005;90:4803-8.
  • Valdivielso JM, Fernandez E. Vitamin D receptor polymorphisms and diseases. Clin Chim Acta 2006;371:1-12.
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Food - Gene Interaction

Including nutraceutical - gene interactions


Nordic Naturals ProDHA

Pharmaceutical Grade [pure] fish oil