CYP3A5 and NAT2 gene polymorphisms: role in childhood acute lymphoblastic leukemia risk and treatment outcome.
Susceptibility to acute lymphoblastic leukemia can be highly influenced by genetic polymorphisms in metabolizing enzyme genes of environmental carcinogens. This study aimed to evaluate the impact of the CYP3A5 and NAT2 metabolizing enzyme polymorphisms on the risk of childhood acute lymphoblastic leukemia. The analysis was conducted on 204 ALL patients and in 364 controls from a Brazilian population, using PCR-RFLP. The CYP3A5 3 polymorphic homozygous genotype was more frequent among ALL patients and the 3 allele variant was significantly associated with increased risk of childhood ALL (OR = 0.29; 95% CI, 0.14-0.60). The homozygous polymorphic genotype for the 6 allele variant was extremely rare and found in only two individuals. The heterozygous frequencies were similar for the ALL group and the control group. No significant differences were observed between the groups analyzed regarding NAT2 variant polymorphisms. None of the polymorphisms analyzed was related to treatment outcome. The results suggest that CYP3A5 3 polymorphism may play an important role in the risk of childhood ALL.
Department of Pediatrics, School of Medicine of Ribeirao Preto, University of São Paulo, Av. Bandeirantes, 3900, HCFMRP-Bloco G, 1A, Sl 218. Bairro Monte Alegre, CEP 14049-900, Ribeirão Prêto, SP, Brazil. nessateruel@yahoo.com
Vanessa S
VS
Silveira
Renata
R
Canalle
Carlos Alberto
CA
Scrideli
Rosane G P
RG
Queiroz
Luiz Fernando
LF
Lopes
Luiz Gonzaga
LG
Tone
D001191:Arylamine N-Acetyltransferase / Q000097:blood / Q000235:genetics*; D001938:Brazil; D051544:Cytochrome P-450 CYP3A / Q000097:blood / Q000235:genetics*; D018572:Disease-Free Survival; D005006:Ethnicity; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000097:blood / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors; D016896:Treatment Outcome
C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human