title: Pharmacogenetics of genes across the doxorubicin pathway.
abstract: BACKGROUND
  A large number of genetic polymorphisms have been reported in the genes that mediate the metabolism, transport and pharmacological activity of doxorubicin. The clinical significance of these is still undergoing evaluation.
  
  
  METHODS
  Doxorubicin is a widely used anticancer drug in the treatment of solid tumors and leukemias. It is a drug characterized by inter-individual variation in pharmacokinetic parameters as well as variation in efficacy and toxicity. It has been hypothesized that variation in genes with a function in doxorubicin pharmacology may contribute to this variation in doxorubicin pharmacology. There is evidence that genetic variants effect the expression of proteins associated with the transport, metabolism and mechanism of action of doxorubicin, and may influence efficacy and toxicity. For example, single nucleotide polymorphisms (SNPs) in the ABCB1 transporter gene have been shown to influence both pharmacokinetics and outcome following doxorubicin chemotherapy. Similar associations have been described for SNPs in the carbonyl reductase (CRB1 and CRB3) genes.
  
  
  CONCLUSIONS
  Although a number of studies have reported associations between genetic variants and different aspects of doxorubicin pharmacology, these associations are not consistently observed. While such observations give insights into aspects of doxorubicin pharmacology, based on current data genotyping may be of limited clinical utility.
authors.affiliation: Newcastle University, Northern Institute for Cancer Research, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: David
authors.initials: D
authors.lastname: Jamieson
authors.forename: Alan V
authors.initials: AV
authors.lastname: Boddy
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D001692:Biological Transport; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D010597:Pharmacogenetics / Q000379:methods*; D020641:Polymorphism, Single Nucleotide
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; C448939:CRB1 protein, human; C472002:CRB3 protein, human; D005136:Eye Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D004317:Doxorubicin