Abstract
The tumor suppressing protein p53 and its downstream effector p21 play important roles in cell cycle regulation. Deficiency or deactivation of these proteins as a result of gene alterations has been indicated in several cancers. Such genetic variations could be considered as susceptibility indicators in acute lymphocytic leukemia (ALL). Therefore, we investigated the associations between ALL risk and TP53 codon 72, p21 codon 31, and MDM2 SNP309 polymorphisms in an Iranian population. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the MDM2 T309G (rs2279744), TP53 codon Arg72Pro (rs1042522), and p21 Ser31Arg (rs1801270) single nucleotide polymorphisms (SNPs). This study was performed in 115 ALL patients and 115 healthy controls in Khuzestan province in southwest Iran. In the control group and ALL patients, p21 Ser/Arg, and MDM2 TG and GG genotypes were associated with significant 1.81-fold (95% confidence interval CI= 1.008-3.267; P < 0.05), 11.07-fold (95% CI= 5.10-24.05; P < 0.0001), and 19.41-fold (95% CI= 8.56-43.99; P < 0.0001) increased risks for ALL, respectively. The TP53 72 Arg allele was significantly more prevalent in ALL patients (56.96%) than in control subjects (47.39%), and was significantly associated with ALL (OR= 1.47; 95% CI = 1.017-2.121, P < 0.05). The MDM2T309G and the p21 Ser31Arg SNPs indicate a significantly increased risk for developing ALL in Khuzestan province.
Highlights
Leukemia is one of the most prevalent cancers, accounting for 3.2% of total cancer deaths worldwide in 2018 [1], with various incidences in different populations [2]
Rs1042522, and p21 rs1801270, which are involved in the P53 activation pathway, were reported to be associated with leukemia risk
We found significantly increased adult acute lymphocytic leukemia (ALL) risk associated with the homozygous murine double minute 2 gene (MDM2) 309 GG and heterozygous 309 TG genotypes
Summary
Leukemia is one of the most prevalent cancers, accounting for 3.2% of total cancer deaths worldwide in 2018 [1], with various incidences in different populations [2]. Deficiency or deactivation of these proteins as a result of gene alterations has been indicated in several cancers. Such genetic variations could be considered as susceptibility indicators in acute lymphocytic leukemia (ALL). This study was performed in 115 ALL patients and 115 healthy controls in Khuzestan province in southwest Iran. Results: In the control group and ALL patients, p21 Ser/Arg, and MDM2 TG and GG genotypes were associated with significant 1.81-fold (95% confidence interval CI= 1.008-3.267; P 0.05), 11.07-fold (95% CI= 5.10-24.05; P < 0.0001), and 19.41-fold (95% CI= 8.56-43.99; P < 0.0001) increased risks for ALL, respectively. Conclusions: The MDM2 T309G and the p21 Ser31Arg SNPs indicate a significantly increased risk for developing ALL in Khuzestan province
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