Role of CXCL12, TP53 and CYP1A1 gene polymorphisms in susceptibility to pediatric acute lymphoblastic leukemia

Kampouraki,Eleni; Lourou,Marilena; Zervou,Maria I.; Ampazoglou,Evangelia-Dimitra; Yachnakis,Emmanuel; Katzilakis,Nikolaos; Goulielmos,George N.; Stiakaki,Eftichia

doi:10.3892/ol.2021.12920

Role of CXCL12, TP53 and CYP1A1 gene polymorphisms in susceptibility to pediatric acute lymphoblastic leukemia

Authors:
- Eleni Kampouraki
- Marilena Lourou
- Maria I. Zervou
- Evangelia-Dimitra Ampazoglou
- Emmanuel Yachnakis
- Nikolaos Katzilakis
- George N. Goulielmos
- Eftichia Stiakaki
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Affiliations: Department of Pediatric Hematology‑Oncology, University Hospital of Heraklion and Laboratory of Blood Diseases and Childhood Cancer Biology, Medical School, University of Crete, 71003 Heraklion, Greece, Section of Molecular Pathology and Human Genetics, Department of Internal Medicine, Medical School of Crete, University of Crete, 71003 Heraklion, Greece, Laboratory of Bio-Medical Data Analyses, Digital Applications and Interdisciplinary Approaches, University of Crete, 71003 Heraklion, Greece
Published online on: July 13, 2021 https://doi.org/10.3892/ol.2021.12920
Article Number: 659

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Abstract

Acute lymphoblastic leukemia (ALL) is the most common type of childhood leukemia and represents one third of all pediatric malignancies. Epidemiological studies have shown that various genetic factors play a crucial role in leukemogenesis. Recent genetic association studies on cancer risk have focused on the effects of single‑nucleotide polymorphisms (SNPs) in genes that regulate inflammation and tumor suppression, such as chemokines, TP53 and cytochrome P450s (CYPs). Genetic polymorphisms in the 3' untranslated region of the C‑X‑C motif chemokine ligand 12 (CXCL12; rs1801157) and TP53 (rs1042522) genes have been suggested to influence the risk of ALL in children, while other studies have indicated an association between the CYP1 subfamily A member 1 (CYP1A1)^*2C (rs1048943) allele and leukemia risk. The aim of the present study was to investigate the possible association of rs1801157 (CXCL12), rs1042522 (TP53) and rs1048943 (CYP1A1^*2C) SNPs with an increased susceptibility of developing ALL. These SNPs were analyzed in 86 children or adolescent patients with ALL and 125 control subjects by PCR‑restriction fragment length polymorphism and allelic‑specific chain reaction techniques. A higher frequency of CYP1A1^*2C heterozygotes and TP53 rare homozygotes, which include the proline (Pro)/Pro genotype, was observed among children with ALL and control subjects, whereas no significant differences were observed for the CXCL12 SNP. Furthermore, the analysis of various allelic combinations of the aforementioned gene polymorphisms demonstrated a markedly increased risk of developing ALL in children. In conclusion, the present study demonstrated that there was a strong association between CYP1A1^*2C heterozygotes, as well as the TP53 Pro/Pro genotype, and an increased susceptibility for pediatric ALL in Caucasians.

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