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

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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.

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Acknowledgements

The authors would like to thank children and their parents or guardians who made this study possible. Warmest thanks to the staff of the Pediatric Hematology and Oncology Center in the Children’s Hospital of Rabat for their collaboration and helpful assistance. Sincere gratitude to Dr. Laurent Abel, Dr. Stéphanie Boisson-Dupuis and Dr. Jocelyn Quisterbert from Imagine Institute, Paris, France for their valuable revisions. Many thanks to Mohammed Lamssiyeh from the Genetics Unit of Military Hospital Mohammed V for the laboratory assistance. The first author was an Excellence Scholarship holder from the National Center for Scientific and Technical Research (CNRST) of Rabat, Morocco.

Funding

This study was supported by the Genetics Unit of Military Hospital Mohammed V in Rabat, Morocco.

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Authors and Affiliations

  1. Genetics Unit, Military Hospital Mohammed V, Rabat, Morocco

    Hanaa Skhoun & Jamila El Baghdadi

  2. Laboratory of Human Pathologies Biology and Genomic Center of Human Pathologies, Department of Biology, Faculty of Sciences, Mohammed V University, Rabat, Morocco

    Hanaa Skhoun, Youssef Bakri & Nadia Dakka

  3. Pediatric Hematology and Oncology Center, Children’s Hospital, Rabat, Morocco

    Mohammed Khattab

  4. BIOLAB Laboratory, Rabat, Morocco

    Aziza Belkhayat & Zahra Takki Chebihi

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  1. Hanaa Skhoun
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Contributions

HS: patients enrollement, genetic study performance, statistical analysis, data collecting and interpretation, involvement in the literature search and writing of the paper. MK: diagnosis and examination of patients. AB: cytogenetic analysis. ZTC: cytogenetic analysis. YB: study investigation. ND: study investigation. JEB: conceptualization, methodology, study investigation, supervision, statistical analysis, revision and editing of the final version.

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Correspondence to Jamila El Baghdadi.

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Skhoun, H., Khattab, M., Belkhayat, A. et al. Association of TP53 gene polymorphisms with the risk of acute lymphoblastic leukemia in Moroccan children. Mol Biol Rep 49, 8291–8300 (2022). https://doi.org/10.1007/s11033-022-07643-3

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