Common variations within HACE1 gene and neuroblastoma susceptibility in a Southern Chinese population

Abstract

Neuroblastoma is a common fatal pediatric cancer of the developing sympathetic nervous system, which accounts for ~10% of all pediatric cancer deaths. To investigate genetic risk factors related to neuroblastoma, many genome-wide association studies have been performed, and single nucleotide polymorphisms (SNPs) within HACE1 gene have been identified to associate with neuroblastoma risk. However, the association of the HACE1 SNPs with neuroblastoma needs to be validated in Southern Chinese children. We genotyped five SNPs located in the HACE1 gene (rs4336470 C>T, rs9404576 T>G, rs4079063 A>G, rs2499663 T>C, and rs2499667 A>G) in 256 Southern Chinese patients in comparison with 531 ethnically matched healthy controls. Single locus analysis showed no significant association between any of HACE1 SNPs and neuroblastoma risk in Southern Chinese children. However, when all the risk genotypes were combined, we found a borderline significant trend toward an increased neuroblastoma risk with 4–5 risk genotypes (adjusted odds ratio =1.36, 95% confidence interval =0.98–1.89, P=0.065). Moreover, stratified analysis found that carriers of 4–5 risk genotypes tended to develop neuroblastoma in the retroperitoneal region and have more aggressive tumors, progressing to advanced clinical stages III/IV, when compared with those of 0–3 risk genotypes. In conclusion, HACE1 gene may have weak effect on neuroblastoma risk in Southern Chinese children. Large well-designed studies are needed to strengthen our findings.

Keywords:

• HACE1
• susceptibility
• neuroblastoma
• GWAS
• polymorphism

Supplementary material

Table S1 Characteristics of neuroblastoma cases and cancer-free controls

Acknowledgments

This study was supported by the grant of State Clinical Key Specialty Construction Project (Pediatric Surgery) 2013 (no GJLCZD1301) and the grant of Clinical Medicine Research and Transformation Center of Brain Injury in Premature Infant in Guangzhou (no 520101-2150092). We thank Yanlu Tong, Hongjiao Chen, and Hezhen Wang for their assistance in DNA extraction and medical histories information collection.

Disclosure

The authors report no conflicts of interest in this work.