LIN28A Gene Polymorphisms Modify Neuroblastoma Susceptibility: A Four-centre Case-control Study

Neuroblastoma ranks the most common seen solid tumour in childhood. Overexpression of LIN28A gene has been linked to the development of multiple human malignancies, but the relationship between LIN28A single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility is still under debate. Herein, we evaluated the correlation of four potentially functional LIN28A SNPs (rs3811464 G>A, rs3811463 T>C, rs34787247 G>A, and rs11247957 G>A) and neuroblastoma susceptibility in 505 neuroblastoma patients and 1070 controls from four independent hospitals in China. The correlation strengths were determined by using odds ratios (ORs) and corresponding 95% confidence intervals (CIs). Among these SNPs, rs34787247 G>A exhibited a significant association with increased susceptibility in neuroblastoma (GA vs GG: adjusted OR = 1.30, 95% CI = 1.03-1.64; AA vs GG: adjusted OR = 2.51, 95% CI = 1.36-4.64, AA/GA vs GG: adjusted OR = 1.42, 95% CI = 1.12-1.80, AA vs GG/GA: adjusted OR = 2.39, 95% CI = 1.29-4.42). Furthermore, the combined analysis of risk genotypes revealed that subjects carrying three risk genotypes (adjusted OR = 1.64, 95% CI = 1.02-2.63) are more inclined to develop neuroblastoma than those without risk genotype, and so do carriers of 1-4 risk genotypes (adjusted OR = 1.26, 95% CI = 1.01-1.56). Stratification analysis further revealed risk effect of rs3811464 G>A, rs34787247 G>A and 1-4 risk genotypes in some subgroups. Haplotype analysis of these four SNPs yields two haplotypes significantly correlated with increased neuroblastoma susceptibility. Overall, our finding indicated that LIN28A SNPs, especially rs34787247 G>A, may increase neuroblastoma risk.