Candidate Gene Association Analysis of Neuroblastoma in Chinese Children Strengthens the Role of LMO1

Abstract

Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and the most frequently diagnosed cancer in the first year of life. Previous genome-wide association studies (GWAS) of Caucasian and African populations have shown that common single nucleotide polymorphisms (SNPs) in several genes are associated with the risk of developing NB, while few studies have been performed on Chinese children. Herein, we examined the association between the genetic polymorphisms in candidate genes and the risk of NB in Chinese children. In total, 127 SNPs in nine target genes, revealed by GWAS studies of other ethnic groups and four related lincRNAs, were genotyped in 549 samples (244 NB patients and 305 healthy controls). After adjustment for gender and age, there were 21 SNPs associated with NB risk at the two-sided P < 0.05 level, 11 of which were located in LMO1. After correction for multiple comparisons, only rs204926 in LMO1 remained significantly different between cases and controls (OR = 0.45, 95% CI: 0.31–0.65, adjusted P = 0.003). In addition, 16 haplotypes in four separate genes were significantly different between case and control groups at an unadjusted P value < 0.05, 11 of which were located in LMO1. A major haplotype, ATC, containing rs204926, rs110420, and rs110419, conferred a significant increase in risk for NB (OR = 1.82, 95% CI: 1.41–2.36, adjusted P < 0.001). The major finding of our study was obtained for risk alleles within the LMO1 gene. Our data suggest that genetic variants in LMO1 are associated with increased NB risk in Chinese children.

LMO1 gene polymorphisms contribute to decreased neuroblastoma susceptibility in a Southern Chinese population

“…In the first GWAS carried out in European descent with a total of 1752 neuroblastoma cases and 4171 controls, three SNPs in the CASC15 gene were found to be associated with increased neuroblastoma risk [1]. The association was verified by the replication studies conducted in Italians [23] and Chinese children [18, 24], but not in African-Americans [22]. In the extended GWAS by Wang et al [21], a total of 2251 neuroblastoma patients and 6097 controls of European ancestry were enrolled.…”

LMO1 polymorphisms and the risk of neuroblastoma: Assessment of meta‐analysis of case‐control studies

“…In addition, the rs2168101 and rs3750952 polymorphisms were markedly associated with decreased NB susceptibility in children from North and South China. 29 A significant association between the rs204926 variant and NB susceptibility has been reported, 32 and rs4758051 and rs10840002 polymorphisms were associated with decreased NB. 29 A significant association between the rs204926 variant and NB susceptibility has been reported, 32 and rs4758051 and rs10840002 polymorphisms were associated with decreased NB.…”

Potentially functional polymorphisms in the LIN28B gene contribute to neuroblastoma susceptibility in Chinese children

“…The same study also demonstrated that depletion of LIN28B protein might lead to significant growth inhibition in vitro , and high expression of LIN28B was associated with worse overall survival in primary neuroblastomas . Currently, the association established in this study was only evaluated in Italians and Northern Chinese population . Given the biological importance of LIN28B and its implication in neuroblastomas, we performed the current hospital‐based case–control study to investigated the association between four potentially functional single nucleotide polymorphisms (SNPs) in the LIN28B gene and neuroblastoma susceptibility in Southern Chinese children.…”