Association between TP53 gene ARG72PRO polymorphism and chromosome aberrations in human cancers.
It is well known that the TP53 gene considerably influences on DNA repair processes. Polymorphisms in the TP53 gene, particularly the well-known Arg72Pro in codon 72 of exon 4 (Ex4+119 G>C; rs1042522), can modify the functionality of the p53 protein and activation of DNA repair. Actually, polymorphic variants Arg and Pro were found to have different properties of regulation of TP53-dependent DNA repair target genes, that can effect various levels of chromosome aberrations in cancer patients with these genotypes. Here, we studied frequency of chromatid breaks (CB), chromosome-type aberrations (CTA) and aberrant cells (AC) in cancer patients (n = 102) with various Arg72Pro genotypes. It was shown that the Arg variant of TP53 gene is associated with high frequency of AC and chromatid breaks. That is Arg/Arg carriers have more different chromosome aberrations in comparison to individuals with Arg/Pro and Pro/Pro genotypes (P < 0.05). Conversely, the lowest level of AC and chromatid breaks were detected in cancer patients with the Pro/Pro genotype. A completely unexpected result was that women with Arg/Arg genotype had the most high frequency of CB and AC in comparison to Arg/Pro and Pro/Pro women carriers (P < 0.001). In the group of male patients we did not show any differences in chromosome aberrations between carriers of Arg72Pro genotypes. In conclusion, the TP53 gene Arg72Pro polymorphism appreciably influence on occurrence of chromosome aberrations in cancer.
Litviakov
Nicolay V
NV
Seversk Biophysical Research Centre of the Federal Medico-Biological Agency, Seversk, Russia.
Denisov
Evgeny V
EV
Takhauov
Ravil' M
RM
Karpov
Andrey B
AB
Skobel'skaja
Elena V
EV
Vasil'eva
Elena O
EO
Goncharik
Olesya O
OO
Ageeva
Alena M
AM
Mamonova
Natalya V
NV
Mezheritskiy
Stanislav A
SA
Sevost'janova
Natalya V
NV
Koshel
Andrey P
AP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D005260:Female; D016158:Genes, p53; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000235:genetics*; D011110:Polymorphism, Genetic