Association of p53 rs1042522, MDM2 rs2279744, and p21 rs1801270 polymorphisms with retinoblastoma risk and invasion in a Chinese population

Abstract

Single nucleotide polymorphisms (SNPs) of p53 rs1042522, MDM2 rs2279744 and p21 rs1801270, all in the p53 pathway, which plays a crucial role in DNA damage and genomic instability, were reported to be associated with cancer risk and pathologic characteristics. This case-control study was designed to analyse the association between these SNPs and retinoblastoma (RB) in a Chinese Han population. These SNPs in 168 RB patients and 185 adult controls were genotyped using genomic DNA from venous blood. No significant difference was observed in allele or genotypic frequencies of these SNPs between Chinese RB patients and controls (all P > 0.05). However, the rs1042522 GC genotype showed a protective effect against RB invasion, as demonstrated by event-free survival (HR = 0.53, P = 0.007 for GC versus GG/CC). This effect was significant for patients with a lag time >1 month and no pre-enucleation treatment (P = 0.007 and P = 0.010, respectively), indicating an interaction between p53 rs1042522 and clinical characteristics, including lag time and pre-enucleation treatment status. Thus, the rs1042522 SNP may be associated with RB invasion in the Han Chinese population; however, further large and functional studies are needed to assess the validity of this association.

Figure 1

Typical raw data obtained using the Sequenom MassARRAY system for single nucleotide polymorphisms of (a–c) p53 rs1042522 G/C, (d–f) MDM2 rs2279744 T/G and (g–i) p21 rs1801270 C/A. The blue arrows above the wave peak indicate the resulting genotypes.

Figure 2. Kaplan-Meier analysis of the association of the selected SNPs of p53 pathway genes with event-free survival (EFS) for RB invasion among enucleated patients.

(a) Cumulative EFS curve of the enucleated patients for the three genotypes of p53 rs1042522 (P = 0.001 for GC versus GG, P = 0.914 for CC versus GG, and P = 0.003 for GC versus CC); (b) Cumulative EFS curve of enucleated patients according to the over-dominant genetic model of p53 rs1042522 (P = 0.000 for GC versus GG/CC). (c) Cumulative EFS curve of enucleated patients according to the three genotypes of MDM2 rs2279744 (P = 0.204 for TG versus TT, P = 0.265 for GG versus TT, and P = 0.940 for TG versus GG); (d) Cumulative EFS curve of enucleated patients according to the three genotypes of p21 rs1801270 (P = 0.524 for CA versus CC, P = 0.614 for AA versus CC, and P = 0.938 for CA versus AA).