Problems of Radiation Medicine and Radiobiology

GENE POLYMORPHISMS OF P53-MEDIATED APOPTOSIS IN CHRONIC LYMPHOCYTIC LEUKEMIA PATIENTS: FEATURES OF DISTRIBUTION DEPENDING ON RADIATION FACTOR IN ANAMNESIS

N. I. Bilous, I. V. Abramenko, A. A. Chumak, I. S. Dyagil, Z. V. Martina
State Institution “National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine”, Melnykov str., 53, Kyiv, 04050, Ukraine

Objective. To set of p53-mediated apoptosis gene polymorphisms (TP53 codon 72 Arg/Pro, р21 codon 31 Ser/Arg, MDM2 SNP309) for the occurrence of CLL in patients who were exposed to ionizing radiation (IR) from the Chornobyl accident.
Methods. Polymorphisms of p53-mediated apoptosis were determined in 320 patients with CLL of B-cell origin: 107 irradiated by the Chornobyl accident patients, 213 patients with CLL who had no history of exposure to IR, 73 individuals without a cancer and hematologic diseases that were affected by the Chornobyl disaster and 72 residents of Kyiv without affecting by IR in anamnesis. Determination of polymorphisms of p53-mediated apoptosis was performed by polymerase chain reaction followed by restriction.
Results. The distribution of genotypes in patients with CLL did not differ from controls, except for reduced the frequency of homozygotes Arg/Arg TP53 among patients with CLL (p = 0.01). Compared with non-irradiated CLL patients in the subgroup of patients affected by the accident, an increase in the frequency of polymorphic alleles of the gene р21 (p = 0.033) was found, especially in combination with Arg allels (genotypes Arg/Arg and Arg/Pro) of TP53 gene and genotype TT SNP309 of MDM2 gene (p = 0.009).
Conclusion. Preliminary studies indicated the likely contribution of rs1801270 polymorphism of the gene р21 in the pathogenesis of CLL in patients who had been exposed to IR. The effects of SNPs rs1042522 of TP53 gene and SNP309 of MDM2 gene on the risk of CLL in the Chornobyl accident sufferers were not revealed.

Key words: chronic lymphocytic leukemia, p53-mediated apoptosis, polymorphism, TP53, р21, MDM2 genes, ionizing radiation.

Problems of radiation medicine and radiobiology. 2014;19:223–230.