Study Of Glucocorticoid Receptor Gene Polymorphism And The Relationship Between Childhood Acute Lymphoblastic Leukemia

Objective Glucocorticoid (GC) is one of the most important drugs in the treatment of childhood acute lymphoblastic leukemia (ALL). Its effect is mediated by Glucocorticoid receptor (GR). Glucocorticoid receptor gene (NR3C1) polymorphisms of GR are correlated with altered sensitivity to GC. In this study, we analyzed SNaPshot SNP genotyping in childhood ALL cases and detected glucocorticoid receptor gene polymorphism BelⅠ(rs41423247), rs4607376, N363S (rs56149945), ER22 (rs6189),9β(rs6198) with single-nucleotide polymorphism (SNP). The study showed it’s uncorrected with clinical features and prognosis of childhood ALL.Subjects and Methods We selected ALL cases that were diagnosed and treated in the hematology ward from January 2004 to September 2010. The samples were obtained from peripheral blood and genome DNA was extracted. We applied methods of SNaPshot SNP genotyping to detected GR gene polymorphism point BelⅠ, rs4607376, N363S, ER22 and 9βsingle-nucleotide polymorphisms. Finally, we analyzed the relationship between GR gene polymorphism and the the clinical features and outcomes of children ALL.Results 1. From Jun 2004 to Sept 2010,105 newly diagnosed patients with childhood ALL in the Hematology and Oncology Centre of our hospital were enrolled into the study with 63 males and 42 females. Their age was from 1 year to 12 years and 4 months (median 4 years and 5 months). Cases were divided into three groups, which were the standard-risk group of 43 cases, the median-risk group of 44 cases and the high-risk group of 18 ones. We found that the remission induction prednisone window test positive in 7 cases (6.6%),15 days without complete remission in 20 cases (19%),33 days without complete remission in 3 cases (3%). Following-up to September 30,2011, the median follow-up time was 41 months (12 to 93 months), of which 19 (18%) patients relapsed,13 patients (12%) died, three were lost.3-year EFS rate is 83%±4%, and 5-year EFS rate is73%±5%.2. We analyzed the glucocorticoid receptor gene 5 loci SNP respectively. The BelⅠis found in three genotypes CC, CG and GG, C allele frequency is 0.22; G is 0.78. rs4607376 genotype existed is AA, AG and GG, A allele frequency is 0.42; G is 0.58. N363S, ER22 and 9(3 were only found a genotype:AA, GG and AA.3. We studied the relationship between BelⅠpolymorphism and acute lymphoblastic leukemia. No statistical difference could be found between the group of CC and CG+GG in terms of sex, immunophenotype, risk group, the initial issuance of the clinical features associated leukocyte. Between the two groups in the induction of remission induction prednisone experimental results, the first 15 days and 33 of the treatment results were analyzed, the difference was not statistically significant. There was also no significant difference between the two groups in the study of relapse. Kaplan-Meier estimates of survival probabilities for patients with acute lymphoblastic leukemia (ALL), according to rs 41423247, the p-value, estimated by log-rank test for the survival differences between the patient groups was not statistically significant.4. We studied the relationship between rs4607376 polymorphism and clinical outcomes of children acute lymphoblastic leukemia. No statistical difference was found between the group of GG and AG+AA in terms of gendar, immunophenotype, risk group classification, the initial white leukocyte counts. Between both groups in the induction of remission induction prednisone experimental results, the first 15th days and 33rd day of the treatment results were analyzed, the difference was not statistically significant. There was also no significant difference between the two groups in the study of relapse. Kaplan-Meier estimates of survival probabilities for patients with acute lymphoblastic leukemia (ALL), according to rs46073767, the P-value, estimated by log-rank test for the survival differences between the patient groups was not statistically significant.Conclusions 1. Glucocorticoid receptor gene locus BelⅠ, rs4607376 in our Chinese children ALL in the performance of single nucleotide polymorphisms exist.2. Glucocorticoid receptor gene locus N363S, ER22 and 9βin our Chinese children ALL didn’t find mutant gene.3. There was no relationship between GR gene locus BelⅠ, rs4607376 gene polymorphism and clinical features and outcomes of Chinese childhood ALL.