Risk Prediction Of Association Genes In Children With Acute Lymphoblastic Leukemia

Objective:Acute lymphoblastic leukemia is the most common malignant tumor in children and the peak age is between 2 and 5 years old.The etiology of childhood ALL is unknown,but it is considered to be affected by genetic factors and environmental factors.We screened 7 genes associated with ALL in European children through literature(ARID5B,CDKN2A,CEBPE,IKZF1,INTS10,OR8U8,TP63)and discussed the associations between 8 single nucleotide polymorphisms of these seven genes(rs7089424 and rs10994982 in ARID5B;rs3731217 in CDKN2A;rs4982731 in CEBPE;rs11978267 in IKZF1;rs920590 in INTS10;rs1945213 in OR8U8;rs17505102 inTP63)and ALL in the Chinese Han nationality children which may help to elucidate the pathogenesis of ALL.Method:A total of 190 pediatric patients diagnosed with ALL at the Children’s Hospital from June 2015 to December 2015 were enrolled in this study.The specimens from all these children were collected and the genome DNA was extracted.Then PCR and mass spectrometry method were used for the detection of 8 single nucleotide polymorphisms(rs10994982,rs7089424,rs3731217,rs4982731,rs11978267,rs920590,rs1945213,rs17505102)of the seven genes(ARID5B,IKZF1,CEBPE,CDKNA2A,TP63,OR8U8,INTS10).And the control group included 270 non-ALL children.Moreover,statistical analysis was carried out to analyze the correlations between the 8 single nucleotide polymorphisms of these seven genes and the etiology of childhood acute lymphocytic leukemia(ALL).Furthermore,the relationships between the different genotypes of the same gene and the susceptibility to childhood acute lymphocytic leukemia were also discussed.Result:The clinical characteristics of ALL were obtained.36.8%of the 190 ALL children were 3-6 years,and high hyperdipoidy(chromosome number>50)and TEL/AML 1 fusion gene were two major genetic subtypes of ALL in Chinese children with the precentages of 18.4%and 17.9%,respectively.The allele and genotype frequencies of 8 single nucleotide polymorphisms in the ALL cases and the controls were analyzed.We found that rs10994982 A risk allele and rs7089424 G risk allele in ARID5B were statisticallysignificant between these two groups(rs10994982,P=0.003;rs7089424,P=0.001).And there were also significantly different between the two groups in the distributions of ARID5B rs10994982genotypes AG,AA,GG andARID5Brs7089424TT,GG,GT(rs1 0994982,P=0.0014;rs7089424,P=0.0071).The relationships between 8 single nucleotide polymorphisms and ALL risk stratification,immunophenotype and cytogenetic typing were analyzed.We found that the AA genotype in ARID5B rs10994982 and GT/GG genotype in ARID5B rs7089424 were significantly associated with ALL medium risk and low risk in China(rs10994982 medium risk OR=2.437,95%CI=1.168-5.085,low risk OR=3.550,95%CI=1.501-8.397;rs7089424medium risk OR=1.9%9,95%CI=1.110-3.495,low risk OR=2.157,95%CI=1.130-4.115),And there was no association between these genotypes and ALL highrisk.AG/AA genotypein ARID5B rs10994982 and GT/GG genotypein ARID5B rs7089424 were also associated with childhood B-lineage(B-ALL),but no significant association with childhood T-lineage(T-ALL)(rs 10994982 B-ALL OR=1.724,95%CI=1.070-2.780,T-ALL OR=1.427,95%CI=0.391-5.204;rs7089424 B-ALL OR=1.841,95%CI=1.215-2.790,T-ALL OR=0.985,95%CI=0.341-2.846).The G risk allele in ARID5B rs7089424 was significantly associated with childhood B-hyperdiploid ALL(P<0.05),but no significant association was identified in ARID5B rs10994982 A risk allele.No significant differences in allele and genotype distributions of these SNPS between these two groups(CDKN2A rs3731217,CEBPE rs4982731,IKZF1 rs11978267,INTS10 rs920590,OR8U8 rs1945213 and TP63 rs17505102)were found.Conclusion:1.We found that ARID5B rs7089424 and rs 10994982 may affect the susceptibility of childhood ALL and they were significantly associated with ALL medium risk and low risk as well as B-lineage ALL.2.No significant associations were observed in the allele and genotype frequencies of CDKN2A rs3731217,CEBPE rs4982731,IKZF1 rs11978267,INTS10 rs920590,OR8U8 rs1945213 and TP63 rs17505102 in China childhood ALL.