Seversk Biophysical Research Centre of the Federal Medico-Biological Agency, Seversk, Russia.
Mol Carcinog. 2010 Jun;49(6):521-4. doi: 10.1002/mc.20633.
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.
众所周知，TP53 基因对 DNA 修复过程有很大影响。TP53 基因的多态性，特别是外显子 4 中密码子 72 处的著名 Arg72Pro（Ex4+119 G>C；rs1042522），可以改变 p53 蛋白的功能和 DNA 修复的激活。实际上，已经发现 Arg 和 Pro 多态性变体具有不同的调节 TP53 依赖性 DNA 修复靶基因的特性，这会影响具有这些基因型的癌症患者中各种染色体畸变的水平。在这里，我们研究了具有不同 Arg72Pro 基因型的癌症患者（n = 102）中染色单体断裂（CB）、染色体型畸变（CTA）和异常细胞（AC）的频率。结果表明，TP53 基因的 Arg 变体与 AC 和染色单体断裂的高频率相关。也就是说，Arg/Arg 携带者与 Arg/Pro 和 Pro/Pro 基因型个体相比，具有更多不同的染色体畸变（P < 0.05）。相反，在具有 Pro/Pro 基因型的癌症患者中，检测到最低水平的 AC 和染色单体断裂。出乎意料的结果是，与 Arg/Pro 和 Pro/Pro 女性携带者相比，Arg/Arg 基因型的女性具有最高的 CB 和 AC 高频率（P < 0.001）。在男性患者组中，我们没有显示出 Arg72Pro 基因型携带者之间染色体畸变的任何差异。总之，TP53 基因 Arg72Pro 多态性明显影响癌症中染色体畸变的发生。
