title: Correlation of CYP2B6, CYP2C19, ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients.
abstract: CYP2B6, CYP2C19, ABCC4, and SOD2 have been implicated in adverse drug reactions and survival after cyclophosphamide (CPA) treatment. 110 BMT patients who received high dose CPA treatment were genotyped for variants in these genes and the results were correlated with toxicity and relapse. CYP2B6 genotype significantly influenced overall toxicity suggesting active CYP2B6 alleles led to higher rates of overall toxicity. The p.R487C deficiency allele was significantly associated with a lower rate of overall toxicity and a higher rate of relapse. SOD2 rs4880 V16A polymorphism was associated with significantly less CPA-related overall toxicity and significantly lower relapse rates by Kaplan-Meier analysis although the SOD2 finding regarding relapse was not significant when evaluated by the cumulative incidence function.
authors: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN, USA. black.john@mayo.edu
authors: John L
authors: JL
authors: Black
authors: Mark R
authors: MR
authors: Litzow
authors: William J
authors: WJ
authors: Hogan
authors: Dennis J
authors: DJ
authors: O'Kane
authors: Denise L
authors: DL
authors: Walker
authors: Timothy G
authors: TG
authors: Lesnick
authors: Walter K
authors: WK
authors: Kremers
authors: Rajeswari
authors: R
authors: Avula
authors: Rhett P
authors: RP
authors: Ketterling
mesh_terms: D000293:Adolescent; D000328:Adult; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001803:Blood Transfusion / Q000379:methods; D016026:Bone Marrow Transplantation / Q000379:methods; D002648:Child; D002675:Child, Preschool; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D006801:Humans; D007223:Infant; D007938:Leukemia / Q000175:diagnosis / Q000235:genetics / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics*; D010089:Oxidoreductases, N-Demethylating / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011379:Prognosis; D013482:Superoxide Dismutase / Q000235:genetics*; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult; D000099156:Superoxide Dismutase 2
chemical_list: D001189:Aryl Hydrocarbon Hydroxylases; D065702:Cytochrome P-450 CYP2B6; D065731:Cytochrome P-450 CYP2C19; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D010089:Oxidoreductases, N-Demethylating; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C073492:ABCC4 protein, human; C585599:CYP2B6 protein, human; C045793:CYP2C19 protein, human