Association of rs11801299 and rs1380576 polymorphisms at MDM4 with risk, clinicopathological features and prognosis in patients with retinoblastoma

Background: rs11801299 and rs1380576, two novel polymorphisms in MDM4 gene, have been investigated in several different cancer types. However, the role of these two polymorphisms in retinoblastoma (RB) remains unclear. Methods: A total of 126 patients with primary RB and 148 age-/gender-matched controls were included in this retrospective study. The frequency of rs11801299 and rs1380576 were determined between RB patients and controls. The association of these two polymorphisms with clinicopathological characteristics, prognosis were further evaluated. Results: AA genotype at rs11801299 was significantly associated with an increased risk of developing RB (OR = 2.06, 95%CI 1.09-3.90). The possibility of developing RB was also significantly increased in individuals with A allele at rs11801299 (OR = 1.49, 95%CI 1.06-2.08). RB patients carrying AA genotype and A allele at rs11801299 were more likely to have tumor invasion and poor differentiation. As for rs1380576, a significantly lower risk of developing RB was observed in patients with G allele (CG + GG) compared with wild-type CC genotype (OR = 0.59, 95%CI 0.36-3.95). RB patients with GG genotype or G allele had a lower risk of developing highly aggressive cancer. Kaplan-Meier curves and log-rank results revealed that RB patients carrying AA genotype or A allele (AA + GA) at rs11801299 had significantly poorer prognosis. Multivariate COX analysis showed that the rs11801299 G allele was associated with decreased survival but was not an independent prognostic factor. Conclusion: rs11801299 was significantly associated with RB risk, pathological differentiation, tumor aggressiveness and poor prognosis.