Genetic susceptibility to retinoblastoma: A meta-analysis of single-nucleotide polymorphisms across global populations

The effect of single-nucleotide polymorphisms (SNPs) in Cyclin Dependent Kinase Inhibitor 1A (CDKN1A C/A), Mouse Double Minute 2 (MDM2), 309 T/G methylenetetrahydrofolate reductase (MTHFR) 677 C/T, MTHFR 1298 A/C, and Methionine synthase (MTR) 2756 A/G has been investigated in retinoblastoma (RB) with inconsistent results. Therefore, this study aims to conduct a meta-analysis and explore the overall role of these genetic variants with retinoblastoma risk. Literature search was done using PubMed, EMBASE, Cochrane Library, Google, Dogpile, and CBM all studies evaluating the association between CDKN1A or p21 C/A, MDM2 309 T/G, MTHFR 677 C/T, MTHFR 1298 A/C, and MTR 2756 A/G polymorphism and RB risk were included. A total of 1773 patients and 2474 controls were included. To understand these polymorphisms' role in RB risk, pooled odds ratio (OR) and 95% confidence interval (CI) were calculated using a random or fixed effects model. P values < 0.05 were considered statistically significant. Funnel plots were used to assess publication bias. Our meta-analysis showed a significant association between RB susceptibility to CDKN1A dominant model (OR = 1.518, 95% CI = 1.003-2.298, P = 0.048), MDM2 dominant model (OR = 0.700, 95% CI = 0.542-0.903, P = 0.006) and MTR 2756 A/G all models that is allele model (OR = 4.680, 95% CI = 1.992-10.993, P = 0.000), dominant model (OR = 2.044, 95% CI = 1.511-2.765, P = 0.000), and recessive model (OR = 0.283, 95% CI = 0.122-0.656, P = 0.003). The present meta-analysis suggested that MTR 2756 A/G, MDM2 309 T/G, and CDKN1A polymorphism are associated with the risk of RB.