ABSTRACT
Objective To investigate the association between single nucleotide polymorphisms (SNP) and its haplotypes of methylenetetrahydrofolate reductase (MTHFR) gene with high dose methotrexate (HDMTX)-induced toxicity in children with acute lymphoblastie leukemia (ALL).Methods HDMTX-treated children with ALL (1.2 to 14-years old) were selected from inpatient and followed for a retrospective study.The toxicity response of HDMTX chemotherapy was evaluated using WHO common toxicity criteria.Sixty-one patients with therapy-related toxicity and 36 patients without therapy-related toxicity were genotyped for 2 ShP (677C＞T and 1298A＞C) of the MTHFR gene by polymerase chain reaction-restriction fragment length polymorphism.Frequency of haplotypes and linkage disequilibrium of MTHFR gene were analyzed by SHEsis program.Results The distribution of MTHFR gene 677C＞T polymorphism did not appeare different between groups with or without toxicity response (x2=4.609,P=0.100),but the 1298A＞C polymorphism was significantly different (x2=10.192,P=0.006).Individuals who carried C allele (AC +CC genotype) had a decreased risk of toxicity response compared to AA genotype ( OR=0.245,95％CI:0.099-0.607,P=0.002).677C＞T and 1298A＞C polymorphisms showed strong linkage disequilibrium (D'=0.895 ).The CC haplotype was significantly associated with decreased risk of toxicity response (OR=0.338,95％CI:0.155-0.738,P=0.005),while the TA haplotype was significantly associated with the increased risk of toxicity response (OR=1.907,95％ CI:1.045-3.482,P=0.035).Conclusion MTHFR gene 1298C allele and CC haplotype might serve as protective factors while TA haplotype as a risk factor for the susceptibility to toxicity response of HDMTX chemotherapy in children with ALL.
ABSTRACT
Objective To evaluate the association between polymorphism of 5,10-methylenetrahydrofolate reductase C677T and risk of acute lymphoblastic leukemia (ALL).Methods Electronic search strategy was carried out among the databases from home and abroad to collect qualified research papers,according to the inclusion and exclusion criteria.Data on case-control studies on association between MTHFR C677T polymorphism and susceptibility to ALL were colleted and analyzed by models of TT vs.CC + CT or TT vs.CC through Meta-analysis.Stratified analysis was carried out according to different age groups (children or adult).Results In systematical analysis,the pooled odds ratios of MTHFR C677T genetype TT vs.CC + CT or TT vs.CC were 0.87(0.69-1.09 ) and 0.82 ( 0.63-1.06 ) respectively; in children' s group,the pooled odds ratios of MTHFR C677T genetype TT vs.CC + CT or TT vs.CC were 0.92 ( 0.79-1.08),0.88 ( 0.75-1.05 ) while in adult group,the pooled odds ratios of MTHFR C677T genetype TT vs.CC + CT or TT vs.CC were 0.45(0.26-0.77),and 0.41 (0.22-0.72) respectively.Conclusion The MTHFR gene 677T variant might not be associated with the risk of children's ALL but might be associated with a reduced risk on adult's ALL.