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 involvedin multiple cellular processes, including transcription, DNA repair, genomic stability, senescence, cell cycle controland apoptosis. A common single nucleotide polymorphism located within the proline rich region of TP53 gene atcodon 72 in exon 4 encodes either proline or arginine. TP53 Arg 72 is more active than TP53 Pro 72 in inducingapoptosis. The aim of this study was to understand the association of the 72 codon polymorphism with acuteleukemia development and prognosis. A total of 288 acute leukemia cases comprising 147 acute lymphocyticleukemia (ALL) and 141 acute myeloid leukemia (AML), as well as 245 controls were recruited for analysis ofthe TP53 72 polymorphism using PCR-RFLP method. Significant association of homozygous arginine genotypewith 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 genotypewas observed. In contrast, AML patients with Pro/Pro had elevated WBC, Blast%, LDH levels with slightlyreduced DFS. Our study indicates that Arg/Arg genotype might confer increased risk to development of acutemyeloid leukemia.