title: In interaction with gender a common CYP3A4 polymorphism may influence the survival rate of chemotherapy for childhood acute lymphoblastic leukemia.
abstract: CYP3A4 has an important role in the metabolisms of many drugs used in acute lymphoblastic leukemia (ALL) therapy; still, there are practically no publications about the role of CYP3A4 polymorphisms in ALL pharmacogenomics. We genotyped eight common single-nucleotide polymorphisms (SNPs) in the CYP3A4 and CYP3A5 genes in 511 children with ALL and investigated whether they influenced the survival of the patients. We involved additional 127 SNPs in 34 candidate genes and searched for interactions with respect to the survival rates. Significant association between the survival rates and the common rs2246709 SNP in the CYP3A4 gene was observed. The gender of the patients and the rs1076991 in the MTHFD1 gene strongly influenced this effect. We calculated new risk assessments involving the gender-rs2246709 interaction and showed that they significantly outperformed the earlier risk-group assessments at every time point. If this finding is confirmed in other populations, it can have a considerable prognostic significance.
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: A
authors.initials: A
authors.lastname: Gézsi
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: O
authors.initials: O
authors.lastname: Lautner-Csorba
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: D J
authors.initials: DJ
authors.lastname: Erdélyi
authors.affiliation: Department of Measurement and Information Systems, University of Technology and Economics, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Hullám
authors.affiliation: Department of Measurement and Information Systems, University of Technology and Economics, Budapest, Hungary.
authors.forename: P
authors.initials: P
authors.lastname: Antal
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: Á F
authors.initials: ÁF
authors.lastname: Semsei
authors.affiliation: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary.
authors.forename: N
authors.initials: N
authors.lastname: Kutszegi
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: M
authors.initials: M
authors.lastname: Hegyi
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: K
authors.initials: K
authors.lastname: Csordás
authors.affiliation: 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary.
authors.forename: G
authors.initials: G
authors.lastname: Kovács
authors.affiliation: 1] Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary [2] Heim Pal Children Hospital, Budapest, Hungary [3] Csertex Research Laboratory, Budapest, Hungary.
authors.forename: C
authors.initials: C
authors.lastname: Szalai
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005783:Gender Identity; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality*; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D015778:Minor Histocompatibility Antigens; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; C539735:MTHFD1 protein, human; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP)