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.
ABSTRACT
The aim of this study was to evaluate the effects of antenatally administered glucocorticoids on bone status of preterm infants at 1 year corrected age. The study population consisted of 32 preterm infants with a gestational age of 24-34 weeks. The infants were divided into two groups according to antenatal exposure to corticosteroids. Quantitative ultrasound (QUS) assessment of bone was performed in the study infants at the corrected age of 1 year. Blood levels of carboxy-terminal propeptide of type I procollagen (PICP) and carboxy-terminal telopeptide of type I collagen (ICTP) were measured at birth and at 1 year corrected age. Levels of PICP and ICTP were significantly lower at birth in corticosteroid-exposed neonates (P < 0.05). At corrected age of 12 months ICTP levels remained significantly lower in corticosteroid-exposed infants, but we found no significant difference in levels of the bone-formation marker PICP between corticosteroid-exposed and nonexposed infants. In the majority of participant preterm infants bone speed of sound (SOS) was within age-adjusted normal values of full-term infants. There was no significant difference in bone SOS between exposed and nonexposed infants at corrected age of 12 months. There was no correlation between SOS and levels of bone markers. The results of our study indicate that, despite the suppression of fetal bone turnover at birth in corticosteroid-exposed infants, antenatal glucocorticoid treatment seems to have no long-term impact on bone status of preterm infants assessed by QUS complementary to measurement of bone-turnover markers at 1 year corrected age.
