ABSTRACT
Objective To investigate the single nucleotide polymorphism(SNP)in the coding region in cyto-chrome P4501 A1 (CYP1A1)gene and to evaluate the contributions of SNPs to acute lymphocytic leukemia(ALL)and acute myeloid leukemia(AML)susceptibility in children.Methods One hundred and twenty -one(male 76,female 45)children with acute leukemia were selected from Department of Hematology in Shenzhen Children′s Hospital,Zuyi Medical College between January 2007 and January 201 4 as the case study group,and the average age was 4.42 years old.Case study group included 1 01 (male 65,female 36,average age 4.38 years old)ALL children (ALL group)and 20(male 1 1 ,female 9,average age 4.66 years old)AML children(AML group).A total of 1 1 6(male 74,female 42) children with respiratory tract infections on health examination during the same period were selected as the control group and the average age was 3.93 years old.SNPs in the coding region in CYP1A1 gene were detected by reverse transcrip-tional(RT)-PCR -denaturing gradient gel elelctrphoresis(DGGE)combined with direct sequencing in the case study group and the control group.Results Only one SNP,A4889G,was screened in the open reading frame (ORF)of CYP1A1 gene in Chinese Han children and the G allele frequency of CYP1A1 gene in the case group,ALL group,AML group and the control group were 31 .4%,32.2%,27.5% and 38.8%.The CYP1A1 A4889G AG and AG +GG geno-type were linked with decreased risk of AML(OR =0.31 ,95%CI:0.1 1 -0.87,P =0.02;OR =0.35,95%CI:0.1 4 -0.93,P =0.03)especially in boys with AML(OR =0.1 2,95%CI:0.03 -0.60,P =0.01 ;OR =0.1 6,95%CI:0.04 -0.65,P =0.01 ),but the CYP1A1 A4889G polymorphism was not associated with the risk of ALL(P >0.05). The CYP1A1 A4889G allele frequency and the distribution of genotypes were significantly different from those reported in America,India,Korea,Brazil and Iran(all P <0.05).Conclusions CYP1A1 A4889G polymorphism may be not as-sociated with susceptibility to ALL,but may decrease the risk of childhood AML especially in boys with AML.In addi-tion,it may exhibit an ethnic difference.
ABSTRACT
Objective To investigate the association between CYP1A1 gene polymorphism and toxicities related to high-does methotrexate of childhood acute leukemia. Methods The SNPs were detected by reverse transcriptional (RT)-PCR-denaturing gradient gel elelctrphoresis combined with direct sequencing in 51 children with acute leukemia. Toxicities were collected thereby. Results Only one SNP,A4889G, was screened in CYP1A1. A4889G polymorphism was not associated with all the toxicities (P > 0.05). High-risk ALL children were more likely to increase the risk of thrombocytopenia compared with standard-risk ALL (P< 0.05). Conclusions CYP1A1 A4889G polymorphism may be not association with all toxicities after HD-MTX ,but the thrombocytopenia may be relevant to the risk degree of ALL children.
ABSTRACT
Objective:To investigate the association between glutathione S-transferase pi (GSTP1) gene polymorphism and toxici-ties related to high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:GSTP1 genotypes and allelic frequencies in 51 children with ALL were determined by Nest PCR, denaturing gel gradient electrophoresis (DGGE), and DNA sequencing. HD-MTX adverse reactions were analyzed using the National Cancer Institute Common Toxicity Criteria (NCICTC). Results:We identified three SNPs of GSTP1, including rs1695 (A313G), rs1138272 (G439T), and rs4891 (T555C). The wild types, het-erozygous types, and homozygous types of GSTP1 rs1695/rs4891 polymorphisms were detected in 32 cases (62.7%), 16 cases (31.4%), and 3 cases (5.9%), respectively. GSTP1 rs1695/rs4891 polymorphisms included only one heterozygous type and one homozygous type. The allele frequencies of the three SNPs were 21.6%, 2.9%, and 21.6%. The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 was associated with decrease in the odds of peripheral hemoglobin (OR=0.25, 95%CI=0.06-1.00, P=0.049). The AG+GG/TC+CC genotype of GSTP1 rs1695/rs4891 in standard and intermediate-risk ALL children was significantly correlated with higher odds of gastrointesti-nal toxicity (OR=0.125, 95%CI=0.02-0.78, P=0.026). Conclusion:GSTP1 rs1695 (A313G)/rs4891 (T555C) gene polymorphism is as-sociated with the reduction of peripheral hemoglobin in ALL children and with the odds of gastrointestinal toxicity in standard and inter-mediate-risk ALL children who receive high-dose methotrexate.
ABSTRACT
Objective:To investigate the correlation between polymorphisms of serine hydroxymethyltransferase1 gene and the adverse reactions of high-dose methotrexate (HD-MTX) in children with acute lymphoblastic leukemia (ALL). Methods:A total of 51 patients with ALL were treated with HD-MTX, and clinical manifestations after HD-MTX treatment were evaluated retrospectively. cD-NA was obtained from mRNA. The polymorphisms of SHMT1 gene containing rs1979277, rs3783, rs1979276, and rs12952556 sites were tested by denaturing gradient gel electrophoresis and direct sequencing. Effects of SHMT1 gene polymorphisms on HD-MTX ad-verse reactions were evaluated. Results:Severe adverse reactions in ALL patients treated with HD-MTX appeared to be mainly neutro-penia and hepatoadverse reactions. The frequency distributions of rs3783 (C>G), rs1979276 (C>T), rs12952556 (A>G), and rs1979277 (C>T) were the same. The polymorphisms of rs1979277 showed no correlation with neutropenia (P>0.05) but rs1979277 CT and TT genotypes were correlated with hepatoadverse reactions (CT: OR=0.129, 95% CI: 0.020 to 0.817, P=0.03; TT: OR=0.103, 95% CI:0.017 to 0.620, P=0.013). Conclusion: No correlation was found between the combination of rs1979277, rs3783, rs1979276, rs12952556, and neutropenia, but one or more of these loci may reduce the risk of hepatoadverse reactions.