Abstract
The effect of single nucleotide polymorphisms (SNPs) at MDM2 has been investigated in several cancer types. Three MDM2 SNPs(rs937283, rs2270744 and rs769412) have previously been suggested to be positively correlated with cancer. In this study, we aimed to explore the association of rs937283, rs2270744 and rs769412 polymorphisms with retinoblastoma (RB) risk, clinicopathological characteristics, and prognosis. Compared with wild-type genotype AA at rs937283, individuals carrying AG and GG genotype had a significantly increased risk for developing RB (OR = 1.86, 95% CI 1.13-3.08; OR = 2.48, 95% CI 1.10-5.62, respectively). RB patients with allele G at rs937283 were more susceptible to invasion and high tumor aggression (OR = 2.42, 95% CI 1.43-4.11; OR = 2.15, 95% CI 1.27-3.64, respectively). Kaplan-Meier curves and log-rank results revealed that RB patients harboring genotype GG and G allele at rs937283 had worse survival (P < 0.02 and P < 0.01, respectively). In addition, the A to G substitution at rs937283 significantly enhanced the transcription activity of the MDM2 gene in vitro. In vivo, we found that MDM2 mRNA and protein were overexpressed in individuals who carried the G allele at rs937283. This study suggested that the MDM2 rs937283 polymorphism is a novel functional SNP both in vitro and in vivo as well as a biomarker for poor prognosis in RB.