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Acute lymphoblastic leukemia (ALL) is the most common type of childhood leukemia and represents one third of all pediatric malignancies. Despite the high survival rates (more than 80%), a noteworthy number of children relapse and for them the outcome remains poor. Epidemiological studies that examined possible risk factors of acute leukemias, proved that genetic factors play a crucial role in leukemogenesis. Recent genetic association studies on cancer risk, have focused on the effects of single nucleotide polymorphisms in genes that regulate inflammation and tumor suppression such as chemokines and P450 cytochrome. Chemokines induce the motility of endothelial and tumor cells. CXCL12, a chemokine expressed in various tumors, binds to chemokine receptor 4 (CXCR4) and is considered to play an important role in tumor growth and invasion. The polymorphism rs1801157 of this gene have been investigated concerning the disease pathogenesis. Moreover, CYP1A1 gene belongs to family 1, subfamily 1A1 of cytochrome P450. CYP1A1 protein is a phase I xenobiotic metabolizing enzyme that activates the conversion of environmental chemicals into carcinogens. The above gene contains two important single nucleotide polymorphism, CYP1A1*2A (rs4646903) and CYP1A1*2C (rs1048943), which are associated with an increased risk of leukemia.

Thirty children with B- lineage ALL (19 boys, mean age 6.8 years) were included in the present study and 70 healthy individuals (20 children and 50 adults blood donors) as control group. Genomic DNA was isolated from peripheral blood of participants and was analyzed for the existence of polymorphisms rs1801157 of CXCL12, and CYP1A1*2C (rs1048943) with Polymerase Chain Reaction (PCR). The PCR products were digested with the restriction enzyme MsPI for CXCL12 and BsrDI for CYP1A1. Descriptive statistics and logistic regression analysis were used to examine for differences between children with ALL and controls.

In the CXCL12 loci, the frequencies of AA, AG, and GG genotype were 3.45%, 93.1% and 3.45% in children with ALL, 13.3%, 60.0%, 26.7% in children control group and 4.17%, 45.83% and 50.0% in adult control group respectively. In the CYP1A1 loci, the frequencies of AA, AG, and GG genotype were 13.3%, 86.7% and 0% in children with ALL, 90.0%, 10.0%, 0% in children control group and 81.6%, 16.4% and 2.0% in adult control group respectively. No statistical significant differences in CXCL12 polymorphism were revealed between children with ALL and healthy groups using logistic regression analysis. Regarding CYP1A1 loci, we detected a positive association for the AG polymorphism and ALL [OR: 37.7 (95% CI: 10.81, 131.37), p<0.001 and OR: 58.5 (95% CI: 9.66, 354.12), p<0.001 using only the children’s control group].

A higher frequency of CYP1A1 heterozygote allele was observed among children with ALL compared to controls, whereas no differences were observed regarding CXCL12 polymorphisms. Future studies in larger populations are needed in order to specify the role of the above polymorphism in childhood ALL.