期刊
PHARMACOGENETICS
卷 12, 期 8, 页码 605-611出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/00008571-200211000-00004
关键词
acute lymphoblastic leukemia; children; therapy-related leukemia; chemotherapy
资金
- NCI NIH HHS [CA13959, CA21765, CA29139, CA30969, CA31566, CA32053, CA33606, CA33625, CA36401, CA51001] Funding Source: Medline
- NIGMS NIH HHS [U01 GM61393, U01GM61374] Funding Source: Medline
Therapy-related acute myeloid leukemia and myelodysplastic syndrome (t-ML) are serious complications that affect some patients after acute lymphoblastic leukemia (ALL) treatment. Genetic polymorphisms in the promoter of CYP3A4 (CYP3A4* 1B) and in NAD(P)H:quinone oxidoreductase (NQO1(609)C-->T substitution) have been associated with the risk of t-ML. A polymorphism in CYP3A5 (CYP3A5*3) affects CYP3A activity and the wild-type allele (CYP3A5* 1) is in partial linkage with the CYP3A4* 1B allele. We compared the genotype frequencies for the CYP3A5*3, the CYP3A4* 1B and the NQO1(609) C-->T substitution in 224 children with ALL who did not develop t-ML (controls) and in 53 children with ALL who did develop the complication. The allele frequencies differed significantly among whites, blacks and Hispanics (P < 0.001 for CYP3A5*3, P < 0.001 for CYP3A4* 1B and P = 0.004 for NQO1(609)), thus we performed the comparisons between ALL controls and t-ML patients after accounting for race. We found no differences in the CYP3A4* 1B allele distribution between ALL controls and t-ML patients in whites (P = 0.339, 6.6% vs. 9.8%), blacks (P = 0.498, 93.8% vs. 87.5%) or Hispanics (P = 0.523, 39.1% vs. 25.0%). The frequencies for the (NQO(160)C-->T) allele did not differ between control and t-ML groups in whites (P = 0.191, 35.0% vs. 44.9%), blacks (P = 0.664, 37.5% vs. 37.5%) or Hispanics (P = 0.447, 65.2% vs. 50.0%). We found no differences between the control and t-ML group in the incidence of homozygous CYP3A5*3 genotypes: 82.0% vs. 85.4% in whites (P = 0.403), 6.5% vs. 12.5% in blacks (P = 0.508), and 69.6% vs. 75.0% in Hispanics (P = 0.663). Our data do not support an association between common CYP3A4, NQO1 or CYP3A5 polymorphisms and the risk of t-ML in children treated for ALL.
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