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

PLoS One. 2015 Jun 1;10(6):e0127856. doi: 10.1371/journal.pone.0127856. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Asian People
  • Child, Preschool
  • DNA-Binding Proteins / genetics*
  • Female
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease / genetics
  • Genome-Wide Association Study / methods*
  • Genotype
  • Haplotypes / genetics
  • Humans
  • Infant
  • LIM Domain Proteins / genetics*
  • Linkage Disequilibrium / genetics
  • Male
  • Neuroblastoma / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Transcription Factors / genetics*

Substances

  • DNA-Binding Proteins
  • LIM Domain Proteins
  • LMO1 protein, human
  • Transcription Factors

Grants and funding

This work was supported by Research Funds of Profession Quota Budjet from Beijing Municipal Science and Technology Commission (2013-bjsekyjs-6), National Natural Science Foundation of China (31401067), and Scientific Research Common Program of Beijing Municipal Commission of Education (KM201510025021). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.