APEX1 Polymorphisms and Neuroblastoma Risk in Chinese Children: A Three-Center Case-Control Study.

Jiabin Liu,Wei Jia,Jiwen Cheng,Huimin Xia,Jiao Zhang,Peng Li,Rui-Xi Hua,Jinhong Zhu,Tianyou Yang,Jing He

doi:10.1155/2019/5736175

Abstract

Neuroblastoma is a life-threatening extracranial solid tumor, preferentially occurring in children. However, its etiology remains unclear. APEX1 is a critical gene in the base excision repair (BER) system responsible for maintaining genome stability. Given the potential effects of APEX1 polymorphisms on the ability of the DNA damage repair, many studies have investigated the association between these variants and susceptibility to several types of cancer but not neuroblastoma. Here, we conducted a three-center case-control study to evaluate the association between APEX1 polymorphisms (rs1130409 T>G, rs1760944 T>G, and rs3136817 T>C) and neuroblastoma risk in Chinese children, consisting of 469 cases and 998 controls. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated to evaluate the associations. No significant association with neuroblastoma risk was found for the studied APEX1 polymorphisms in the single locus or combination analysis. Interestingly, stratified analysis showed that rs1130409 GG genotype significantly reduced the risk of tumor in males. Furthermore, we found that carriers with 1-3 protective genotypes had a lower neuroblastoma risk in the children older than18 months and male, when compared to those without protective genotypes. In summary, our data indicate that APEX1 gene polymorphisms may have a weak effect on neuroblastoma susceptibility. These findings should be further validated by well-designed studies with larger sample size.

Highlights

Neuroblastoma is the most frequently diagnosed extracranial pediatric malignancy in children younger than 12 months, which accounts for almost 10% of all pediatric malignancies and 15% of pediatric cancer-related deaths [1]
Neuroblastoma can be classified into low, intermediate, and high-risk groups depending on the clinical feature, pathological phenotypes, and prognostic factors [3]
We further assessed the combined effect of protective polymorphisms of APEX1 gene on neuroblastoma risk

Summary

Introduction

Neuroblastoma is the most frequently diagnosed extracranial pediatric malignancy in children younger than 12 months, which accounts for almost 10% of all pediatric malignancies and 15% of pediatric cancer-related deaths [1]. Neuroblastoma is a highly heterogeneous tumor with a wide range of clinical symptoms. Some patients with innocent tumors have spontaneous regression, while others have poor prognosis even after receiving intensive treatment because of the distant metastasis [2]. Neuroblastoma can be classified into low-, intermediate-, and high-risk groups depending on the clinical feature, pathological phenotypes, and prognostic factors [3]. Despite the great progresses made in multimode treatments for neuroblastoma, the survival rate remains unsatisfying. The overall 5-year survival rate is around 70%; the survival rate for high-risk patients is lower than 40% [4]. This poor prognosis may be partially attributed to widespread metastasis at the time of diagnosis [5]

Methods

Results

Conclusion