Association of TP53 gene polymorphisms with the risk of acute lymphoblastic leukemia in Moroccan children.

ABSTRACT

BACKGROUND: TP53 gene plays a pivotal role in maintaining genetic stability and prevention of malignancies. Alterations of this gene are implicated in more than half of human cancers. To the best of our knowledge, this study is the first to explore TP53 polymorphisms in Moroccan childhood acute lymphoblastic leukemia (ALL). METHODS AND RESULTS: DNA samples of 45 ALL children were obtained from peripheral blood. A total of 333 healthy Moroccans were used as controls. Polymerase chain reaction and Sanger sequencing were performed to analyze TP53 hotspot exons in cases. We identified a significant protective effect of the TP53-Arg variant at rs1042522 [OR 0.4593 (0.249-0.8472), p = 0.0127] and the Pro/Arg genotype [OR 0.0350 (0.0047-0.2583), p = 0.0010]. Additionally, we found a novel association between the C-allele of Arg213Arg 1800372 [OR 2.7736 (1.3821-5.5664), p = 0.0041] and the risk of childhood ALL. Importantly, TC/CC genotypes of this polymorphism were revealed to enhance the risk of ALL among females [OR 9.0 (3.1555-25.6693), p < 0.0001]. Arg213Arg was also noticed to be associated with the hemoglobin count of patients at diagnosis by linear regression (p = 0.0318). The analysis of penetrance showed a significant association of the CG/GG genotypes at rs1042522 and TC/CC genotypes at rs1800372 to childhood ALL via dominant model [OR 0.2090 (0.09074-0.4814), p = 0.0002 and OR 3.4205 (1.6084-7.2742), p = 0.0014 for rs1042522 and rs1800372 respectively]. No association was found between TP53 polymorphisms and patients survival. CONCLUSION: Altogether, our findings indicated that TP53 polymorphisms are significantly involved in the genetic susceptibility to childhood ALL in Morocco.