Association between the TP53 Arg72Pro polymorphism and clinical outcomes in acute myeloid leukemia

Association Analysis of TP53 rs1042522, MDM2 rs2279744, rs3730485, MDM4 rs4245739 Variants and Acute Myeloid Leukemia Susceptibility, Risk Stratification Scores, and Clinical Features: An Exploratory Study

“…Our results showed that the variant genotypes of TP53 rs1042522 are associated with higher odds of AML. Our results regarding AML susceptibility are similar to those reported recently by Bezerra MF et al and Dunna NR et al [11,16]. Studies included in a meta-analysis by Tian X et al [7], investigating the TP53 rs1042522 on AML patients [1,[12][13][14][15], did not find associations between the variant genotypes of TP53 rs1042522 and AML susceptibility, except the study performed by Dunna NR et al [16] on 141 Japanese AML patients.…”

“…Other associations between the investigated variants and genes mutations were not found. The study performed by Bezerra MF et al [11] on 189 Brazilian AML patients investigated the molecular and cytogenetic risk scores according to TP53 rs1042522, but they did not find any associations. The role of TP53 rs1042522 in cancer susceptibility and progression may be explained by the fact that the p53 protein codified by the TP53 gene with wild type genotype of rs1042522, interacts more efficiently with the MDM2 protein and in consequence the apoptosis is more efficient [42].…”

“…MDM2 rs2279744 (MDM2 309T>G) and rs3730485 (MDM2 del1518) and MDM4 rs4245739 (MDM4 34091 C>A) variants were reported to influence the genes activity being associated with carcinogenesis and tumor progression [17][18][19][20]. Moreover, the interaction between TP53 rs1042522 and MDM2 rs2279744 [11,13,29] and between MDM2 rs2279744 and rs3730485 [21] was reported. Therefore, our study evaluated the associations between the mentioned variants and odds of developing AML and the interactions of investigated TP53, MDM2, and MDM4 variants and their association with odds of AML.…”

“…While no association was found between AML risk and variant allele of rs1042522, different associations with OS and response to treatment were noticed. On the other hand, one recent study performed on 189 Brazilian AML patients described an association between rs1042522 and AML risk [11]. One cause of contradictory results may be the small cohorts of the mentioned studies and different ethnicity of the subjects [2,11].…”

“…In malignancies, including leukemia, TP53 gene expression was reported to be affected by a missense variant, rs1042522 (TP53 Arg72Pro) [7,8]. Moreover, the variant allele of rs1042522 was reported to decrease apoptotic activity, increase the risk of cancer (including leukemia), and to be associated with poor overall survival (OS) in patients with AML and higher rate of refractory disease [2,7,[9][10][11].…”