Polymorphisms of xenobiotic metabolizing enzymes and DNA repair genes and outcome in childhood acute lymphoblastic leukemia

Vanessa da Silva Silveira; Renata Canalle; Carlos Alberto Scrideli; Rosane Gomes de Paula Queiroz; Heloisa Bettiol; Elvis Terci Valera; Luiz Gonzaga Tone

doi:10.1016/j.leukres.2008.12.006

Polymorphisms of xenobiotic metabolizing enzymes and DNA repair genes and outcome in childhood acute lymphoblastic leukemia

Leuk Res. 2009 Jul;33(7):898-901. doi: 10.1016/j.leukres.2008.12.006. Epub 2009 Jan 21.

Authors

Vanessa da Silva Silveira¹, Renata Canalle, Carlos Alberto Scrideli, Rosane Gomes de Paula Queiroz, Heloisa Bettiol, Elvis Terci Valera, Luiz Gonzaga Tone

Affiliation

¹ Department of Genetics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil.

PMID: 19162321
DOI: 10.1016/j.leukres.2008.12.006

Abstract

The interindividual variation in the activity of xenobiotic metabolizing enzymes and DNA repair genes could modify an individual's risk of recurrent malignancy and response to therapy. We investigated whether ALL outcome was related to polymorphisms in genes CYP2D6, MPO, EPHX1, NQO1, TS, XPD and XRCC1 in 95 consecutive ALL children by PCR or PCR-FRLP techniques. Polymorphisms in genes NQO1 and TS were associated with a significantly slow response to induction chemotherapy and NQO1 was also associated with a lower five-year event-free survival. This study suggests that polymorphisms of NQO1 and TS could be important for patient response to induction therapy and for treatment outcome.

Publication types

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

MeSH terms

Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Child
Cytochrome P-450 CYP2D6 / genetics
DNA Repair
DNA Repair Enzymes / genetics*
DNA-Binding Proteins / genetics
Epoxide Hydrolases / genetics
Female
Flow Cytometry
Granulocyte Colony-Stimulating Factor / genetics
Humans
Interleukin-3 / genetics
Male
NAD(P)H Dehydrogenase (Quinone) / genetics
Polymorphism, Genetic / genetics*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / genetics*
Precursor Cell Lymphoblastic Leukemia-Lymphoma / pathology
Prognosis
Recombinant Fusion Proteins / genetics
Recombinant Proteins
Remission Induction
Survival Rate
Thymidylate Synthase / genetics
Treatment Outcome
X-ray Repair Cross Complementing Protein 1
Xeroderma Pigmentosum Group D Protein / genetics

Substances

DNA-Binding Proteins
Interleukin-3
Recombinant Fusion Proteins
Recombinant Proteins
X-ray Repair Cross Complementing Protein 1
XRCC1 protein, human
myelopoietin
Granulocyte Colony-Stimulating Factor
Cytochrome P-450 CYP2D6
NAD(P)H Dehydrogenase (Quinone)
NQO1 protein, human
Thymidylate Synthase
Epoxide Hydrolases
EPHX1 protein, human
Xeroderma Pigmentosum Group D Protein
ERCC2 protein, human
DNA Repair Enzymes