THE HOMOZYGOUS TP53 P72R SNP IS ASSOCIATED WITH NON-FAVORABLE CYTOGENETIC RISK GROUPS IN ACUTE MYELOID LEUKEMIA
(Abstract release date: 05/19/16)
EHA Library. Schulz E. 06/09/16; 132483; E934
Dr. Eduard Schulz
Contributions
Contributions
Abstract
Abstract: E934
Type: Eposter Presentation
Background
Previous results about a possible predisposition for acute myeloid leukemia (AML) in individuals with the TP53 P72R SNP are conflicting.
Aims
We tested the hypothesis that the risk for AML development is increased in P72R carriers and that this SNP also influences survival of these patients.
Methods
We performed a case control study of 215 AML patients from Graz, Austria, and Dresden, Germany, and of 3759 controls from Graz and Kiel, Germany. Genotyping was accomplished with constitutional DNA using the TaqMan assay and direct sequencing. The presence of an Hardy-Weinberg equilibrium and the homogeneity of case and control genotypes as well as cytogenetic risk groups according to European LeukemiaNet were tested by the chi-squared test. Survival analyses according to different genotypes stratified for treatment centers were performed by the Kaplan-Meier method and the Wald-test of cox regression. The likelihood ratio test was used to assess the additive model of single alleles.
Results
Genotypes of cases and controls were in Hardy-Weinberg equilibrium (AMLs P=0.192, controls P=0.325; df=1). There was no difference in the genotype distributions between AML patients (PP n=20, PR n=78, RR n=117) and controls (PP n=249, PR n=1482, RR n=2028; P=0.262; df=2). This was also true for the recessive model PP/PR versus RR (P=0.949; df=1). Survival analyses of patients who received at least 3+7 induction therapy showed a trend for better overall survival (OS) in the combined group of patients with the PP/PR genotypes (HR=0.70, 95% CI, 0.46-1.1, P=0.091) whereas no difference was present between all three genotype groups. The additive model of Arginine alleles showed a trend for decreased survival (PP>PR>RR; 72R, HR=1.40, 95% CI, 0.99-1.90, P=0.061). There was no association with relapse free survival. Analyses of clinical parameters of all patients showed a significantly different distribution of cytogenetic risk groups with decrease of favorable cytogenetics in patients with the RR genotype (PP/PR, 15/90 [16.7%]; RR 6/112 [5.4%]; P=0.0171; df=1).
Conclusion
There is no association of the P72R genotype with AML development in this study. The RR genotype shows a trend for lower OS and a statistically significant association with non-favorable cytogenetic risk groups.
Session topic: E-poster
Keyword(s): AML, P53, SNP
Type: Eposter Presentation
Background
Previous results about a possible predisposition for acute myeloid leukemia (AML) in individuals with the TP53 P72R SNP are conflicting.
Aims
We tested the hypothesis that the risk for AML development is increased in P72R carriers and that this SNP also influences survival of these patients.
Methods
We performed a case control study of 215 AML patients from Graz, Austria, and Dresden, Germany, and of 3759 controls from Graz and Kiel, Germany. Genotyping was accomplished with constitutional DNA using the TaqMan assay and direct sequencing. The presence of an Hardy-Weinberg equilibrium and the homogeneity of case and control genotypes as well as cytogenetic risk groups according to European LeukemiaNet were tested by the chi-squared test. Survival analyses according to different genotypes stratified for treatment centers were performed by the Kaplan-Meier method and the Wald-test of cox regression. The likelihood ratio test was used to assess the additive model of single alleles.
Results
Genotypes of cases and controls were in Hardy-Weinberg equilibrium (AMLs P=0.192, controls P=0.325; df=1). There was no difference in the genotype distributions between AML patients (PP n=20, PR n=78, RR n=117) and controls (PP n=249, PR n=1482, RR n=2028; P=0.262; df=2). This was also true for the recessive model PP/PR versus RR (P=0.949; df=1). Survival analyses of patients who received at least 3+7 induction therapy showed a trend for better overall survival (OS) in the combined group of patients with the PP/PR genotypes (HR=0.70, 95% CI, 0.46-1.1, P=0.091) whereas no difference was present between all three genotype groups. The additive model of Arginine alleles showed a trend for decreased survival (PP>PR>RR; 72R, HR=1.40, 95% CI, 0.99-1.90, P=0.061). There was no association with relapse free survival. Analyses of clinical parameters of all patients showed a significantly different distribution of cytogenetic risk groups with decrease of favorable cytogenetics in patients with the RR genotype (PP/PR, 15/90 [16.7%]; RR 6/112 [5.4%]; P=0.0171; df=1).
Conclusion
There is no association of the P72R genotype with AML development in this study. The RR genotype shows a trend for lower OS and a statistically significant association with non-favorable cytogenetic risk groups.
Session topic: E-poster
Keyword(s): AML, P53, SNP
Abstract: E934
Type: Eposter Presentation
Background
Previous results about a possible predisposition for acute myeloid leukemia (AML) in individuals with the TP53 P72R SNP are conflicting.
Aims
We tested the hypothesis that the risk for AML development is increased in P72R carriers and that this SNP also influences survival of these patients.
Methods
We performed a case control study of 215 AML patients from Graz, Austria, and Dresden, Germany, and of 3759 controls from Graz and Kiel, Germany. Genotyping was accomplished with constitutional DNA using the TaqMan assay and direct sequencing. The presence of an Hardy-Weinberg equilibrium and the homogeneity of case and control genotypes as well as cytogenetic risk groups according to European LeukemiaNet were tested by the chi-squared test. Survival analyses according to different genotypes stratified for treatment centers were performed by the Kaplan-Meier method and the Wald-test of cox regression. The likelihood ratio test was used to assess the additive model of single alleles.
Results
Genotypes of cases and controls were in Hardy-Weinberg equilibrium (AMLs P=0.192, controls P=0.325; df=1). There was no difference in the genotype distributions between AML patients (PP n=20, PR n=78, RR n=117) and controls (PP n=249, PR n=1482, RR n=2028; P=0.262; df=2). This was also true for the recessive model PP/PR versus RR (P=0.949; df=1). Survival analyses of patients who received at least 3+7 induction therapy showed a trend for better overall survival (OS) in the combined group of patients with the PP/PR genotypes (HR=0.70, 95% CI, 0.46-1.1, P=0.091) whereas no difference was present between all three genotype groups. The additive model of Arginine alleles showed a trend for decreased survival (PP>PR>RR; 72R, HR=1.40, 95% CI, 0.99-1.90, P=0.061). There was no association with relapse free survival. Analyses of clinical parameters of all patients showed a significantly different distribution of cytogenetic risk groups with decrease of favorable cytogenetics in patients with the RR genotype (PP/PR, 15/90 [16.7%]; RR 6/112 [5.4%]; P=0.0171; df=1).
Conclusion
There is no association of the P72R genotype with AML development in this study. The RR genotype shows a trend for lower OS and a statistically significant association with non-favorable cytogenetic risk groups.
Session topic: E-poster
Keyword(s): AML, P53, SNP
Type: Eposter Presentation
Background
Previous results about a possible predisposition for acute myeloid leukemia (AML) in individuals with the TP53 P72R SNP are conflicting.
Aims
We tested the hypothesis that the risk for AML development is increased in P72R carriers and that this SNP also influences survival of these patients.
Methods
We performed a case control study of 215 AML patients from Graz, Austria, and Dresden, Germany, and of 3759 controls from Graz and Kiel, Germany. Genotyping was accomplished with constitutional DNA using the TaqMan assay and direct sequencing. The presence of an Hardy-Weinberg equilibrium and the homogeneity of case and control genotypes as well as cytogenetic risk groups according to European LeukemiaNet were tested by the chi-squared test. Survival analyses according to different genotypes stratified for treatment centers were performed by the Kaplan-Meier method and the Wald-test of cox regression. The likelihood ratio test was used to assess the additive model of single alleles.
Results
Genotypes of cases and controls were in Hardy-Weinberg equilibrium (AMLs P=0.192, controls P=0.325; df=1). There was no difference in the genotype distributions between AML patients (PP n=20, PR n=78, RR n=117) and controls (PP n=249, PR n=1482, RR n=2028; P=0.262; df=2). This was also true for the recessive model PP/PR versus RR (P=0.949; df=1). Survival analyses of patients who received at least 3+7 induction therapy showed a trend for better overall survival (OS) in the combined group of patients with the PP/PR genotypes (HR=0.70, 95% CI, 0.46-1.1, P=0.091) whereas no difference was present between all three genotype groups. The additive model of Arginine alleles showed a trend for decreased survival (PP>PR>RR; 72R, HR=1.40, 95% CI, 0.99-1.90, P=0.061). There was no association with relapse free survival. Analyses of clinical parameters of all patients showed a significantly different distribution of cytogenetic risk groups with decrease of favorable cytogenetics in patients with the RR genotype (PP/PR, 15/90 [16.7%]; RR 6/112 [5.4%]; P=0.0171; df=1).
Conclusion
There is no association of the P72R genotype with AML development in this study. The RR genotype shows a trend for lower OS and a statistically significant association with non-favorable cytogenetic risk groups.
Session topic: E-poster
Keyword(s): AML, P53, SNP
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