Cytochrome P450 1B1 and 2C9 genotypes and risk of ischemic vascular disease, cancer, and chronic obstructive pulmonary disease

Curr Vasc Pharmacol. 2012 Jul;10(4):512-20. doi: 10.2174/157016112800812746.

Abstract

The aim of this review is to summarize present knowledge of genetic variation in cytochrome P450 1B1 (CYP1B1) and 2C9 (CYP2C9) genes and risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease. The CYP1B1 and CYP2C9 enzymes metabolize polycyclic aromatic hydrocarbons found in tobacco smoke and thereby generate disease-causing metabolites suggested to be important in tobacco-related diseases. Furthermore, CYP1B1 also metabolizes estrogen while CYP2C9 metabolizes arachidonic acid, both creating metabolites potentially important in risk of female cancer or ischemic vascular disease. Genetic variation in genes coding for CYP1B1 and CYP2C9 enzymes have shown altered enzyme activity affecting levels of metabolites and thus potentially risk of disease. So far, however, findings have been inconsistent. Recently, large studies on the association between genetic variation in CYP1B1 and CYP2C9 and risk of disease with considerable statistical power rebutted the hypotheses that these genetic variants affect risk of tobacco-related cancer, female cancer, chronic obstructive pulmonary disease and ischemic vascular disease.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Cytochrome P-450 CYP1B1
  • Cytochrome P-450 CYP2C9
  • Eicosanoids / metabolism
  • Estrogens / metabolism
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Ischemia / enzymology
  • Ischemia / genetics*
  • Ischemia / metabolism
  • Male
  • Metabolic Detoxication, Phase I
  • Neoplasms / etiology
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Polycyclic Aromatic Hydrocarbons / pharmacokinetics
  • Polymorphism, Genetic*
  • Pulmonary Disease, Chronic Obstructive / enzymology
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Smoking / adverse effects
  • Vascular Diseases / enzymology
  • Vascular Diseases / genetics*
  • Vascular Diseases / metabolism

Substances

  • Eicosanoids
  • Estrogens
  • Polycyclic Aromatic Hydrocarbons
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • CYP1B1 protein, human
  • Cytochrome P-450 CYP1B1