TP53 Codon 72 Polymorphism and Risk of Acute Leukemia

Abstract

TP53 is the mostly commonly mutated gene in many cancers and the P53 tumor suppressor protein is involved in multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle control and apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene at codon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducing apoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acute leukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocytic leukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis of the TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotype with AML was observed (χ2-133.53; df-2, p < 0.001. When data were analyzed with respect to clinical variables, elevation in mean WBC, blast %, LDH levels and slight reduction in DFS in ALL cases with the arginine genotype was observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightly reduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acute myeloid leukemia.

The TP53 Pro72Arg SNP in de novo acute myeloid leukaemia – results of two cohort studies involving 215 patients and 3759 controls

“…We found no evidence to support variation at TP53 codon 72 as an independent determinant of de novo AML risk and survival. We could not confirm an association of TP53Arg72 with AML, as shown Dunna et al (), who used, blood samples for genotyping, but timing of collection, i.e. diagnosis or remission, was not stated.…”

“…In de novo AML, results of such studies are hampered by small subject numbers, not providing Hardy–Weinberg equilibrium (HWE), confounding different leukaemia subentities or by selection of inappropriate source materials for genotyping (Ruan et al , ). A case–control study from India, of 141 AML patients and 245 controls, using unspecified blood samples for genotyping showed a significant association of homozygous TP53Arg72 with AML susceptibility [odds ratio (OR) 1·75, 95% confidence interval (CI) 1·14–2·67] (Dunna et al , ). The largest case–control study in AML to date from China using 307 diagnostic bone marrow samples for genotyping and 560 controls showed significantly inferior treatment outcomes in homozygous TP53Arg72 carriers [2‐year overall survival (OS) Pro/Pro and Pro/Arg 45·7% vs. Arg/Arg 16·5%, P = 0·003] but no association with AML development (Shi et al , ).…”

The association between oral anaerobic bacteria and acute myeloid leukemia

“…The frequency of the homozygous Arginine genotype was significantly elevated in the AML group compared to the control group [5].…”

“…It has been observed that the codon 72 polymorphism of p53 has been significantly associated with AML cases compared to controls [5]. The frequency of the homozygous Arginine genotype was significantly elevated in the AML group compared to the control group [5].…”

Hydroxycarbamide for patients with silent cerebral infarcts: outcomes and patient preference

“…In de novo AML, results of such studies are hampered by small subject numbers, not providing Hardy-Weinberg equilibrium (HWE), confounding different leukaemia subentities or by selection of inappropriate source materials for genotyping (Ruan et al, 2015). A case-control study from India, of 141 AML patients and 245 controls, using unspecified blood samples for genotyping showed a significant association of homozygous TP53Arg72 with AML susceptibility [odds ratio (OR) 1Á75, 95% confidence interval (CI) 1Á14-2Á67] (Dunna et al, 2012). The largest case-control study in AML to date from China using 307 diagnostic bone marrow samples for genotyping and 560 controls showed significantly inferior treatment outcomes in homozygous TP53Arg72 carriers [2-year overall survival (OS) Pro/Pro and Pro/Arg 45Á7% vs. Arg/Arg 16Á5%, P = 0Á003] but no association with AML development (Shi et al, 2011).…”