Date Published: March 27, 2018
Publisher: Impact Journals
Author(s): Zhen-Jian Zhuo, Ruizhong Zhang, Jiao Zhang, Jinhong Zhu, Tianyou Yang, Yan Zou, Jing He, Huimin Xia.
Neuroblastoma is the third most common childhood cancer after leukemias and cancer of the central nervous system. Long noncoding RNA MEG3 polymorphisms have been shown to confer cancer susceptibility; however, their roles in the genetic predisposition to neuroblastoma remain unclarified. To answer this question, we genotyped two MEG3 polymorphisms, rs7158663 G>A and rs4081134 G>A, in 392 neuroblastoma children and 783 controls by TaqMan method. The results showed that neither single locus nor the combination analysis supported an association between MEG3 polymorphism and neuroblastoma risk. Interestingly, we found that subjects carrying rs4081134 AG/AA genotypes significantly tended to develop neuroblastoma among subgroups with age >18 month (adjusted OR=1.36, 95% CI=1.01-1.84) and clinical stage III+IV disease (adjusted OR=1.47, 95% CI=1.08-1.99), when compared with reference group. In the combined analysis of MEG3 polymorphisms, we found that carriers of 2 risk genotypes were more likely to have higher risk of developing neuroblastoma than those with 0-1 risk genotype among children more than 18 months of age (adjusted OR=1.36, 95% CI=1.01-1.84, P=0.042), and with clinical stages III+IV disease (adjusted OR=1.47, 95% CI=1.08-2.00, P=0.014). Our data suggest MEG3 as a weak-effect neuroblastoma susceptibility gene. Well-designed studies with large sample studies are needed to further validate this finding.
Neuroblastoma is a heterogeneous tumor rising from neural crest progenitor cells. It is the most common solid neoplasm in children, accounting for nearly 10% of all childhood cancers . Neuroblastoma is characterized by broadly clinical presentation. Some bearing favorable tumors have spontaneous regression without chemotherapy; others have metastatic disease resistant to even intense treatment [2,3]. Survival rates of patients with the most aggressive form of neuroblastoma are less than 40%, even after receiving intensive therapy [1,4,5].
To determine the association of the MEG3 polymorphisms with neuroblastoma risk, we conducted this hospital-based case-control study in Chinese children. Our study provides evidence of the effects of MEG3 polymorphisms on neuroblastoma susceptibility. Neither of the rs7158663 G>A and rs4081134 G>A significantly modifies neuroblastoma risk. Notably, subjects with rs4081134 AG/AA genotypes were more likely to develop neuroblastoma among subgroup with age >18 month and clinical stage III+IV disease.