HOTTIP rs1859168 C > A polymorphism reduces neuroblastoma susceptibility in Chinese children

Eur J Pediatr. 2024 Dec 24;184(1):104. doi: 10.1007/s00431-024-05942-4.

Abstract

Neuroblastoma, " a malignancy originating from neural crest cells, is most commonly diagnosed in children and adolescents. Polymorphisms within the long noncoding RNA (lncRNA) HOXA distal transcript antisense RNA (HOTTIP) are believed to have the capacity to alter an individual's susceptibility to various cancers. This study aimed to investigate the link between HOTTIP gene polymorphisms and neuroblastoma susceptibility. We identified the genotypes of two prevalent polymorphisms (rs3807598 and rs1859168) within the HOTTIP via the TaqMan assay in a cohort comprising 402 individuals diagnosed with neuroblastoma and 473 healthy controls. Logistic regression was used to evaluate the associations between the HOTTIP polymorphisms and the likelihood of neuroblastoma susceptibility. Additionally, the genotype-tissue expression (GTEx) database was used to investigate how these HOTTIP gene variations influence gene expression across different tissues. Our findings demonstrated a significant association between the rs1859168 C > A polymorphism and reduced neuroblastoma susceptibility (CA vs. CC: adjusted odds ratio (OR) = 0.55, 95% confidence interval (CI) = 0.40-0.74, P = 0.0001; CA/AA vs. CC: adjusted OR = 0.69, 95% CI = 0.53-0.91, P = 0.010). The additional stratified analysis revealed that the presence of rs1859168 CA/AA or two protective genotypes was associated with a lower susceptibility in specific subgroups, such as older children and girls. Expression quantitative trait locus (eQTL) analysis revealed that the rs1859168 CC genotype was related to high expression of the HOTTIP gene.

Conclusion: We found that HOTTIP gene polymorphisms were associated with a reduced likelihood of neuroblastoma in Chinese children. Further studies with large cohorts and diverse ethnicities are warranted to verify our results.

What is known: • Genetic variations can influence neuroblastoma susceptibility. HOTTIP gene polymorphisms may alter an individual's susceptibility to various cancers.

What is new: • HOTTIP gene polymorphisms were associated with a reduced risk of neuroblastoma in Chinese children.

Keywords: HOTTIP; LncRNA; Neuroblastoma; Polymorphism; Susceptibility.

MeSH terms

  • Asian People* / genetics
  • Case-Control Studies
  • Child
  • Child, Preschool
  • China / epidemiology
  • East Asian People
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Infant
  • Male
  • Neuroblastoma* / genetics
  • Polymorphism, Single Nucleotide*
  • RNA, Long Noncoding* / genetics

Substances

  • RNA, Long Noncoding
  • long noncoding RNA HOTTIP, human