Abstract
Neuroblastoma is one of the most commonly diagnosed extracranial solid tumors in infancy; however, the etiology of neuroblastoma remains largely unknown. Previous genome-wide association study (GWAS) indicated that several common genetic variations (rs110419 A > G, rs4758051 G > A, rs10840002 A > G and rs204938 A > G) in the LIM domain only 1 (LMO1) gene were associated with neuroblastoma susceptibility. The aim of this study was to evaluate the correlation between the four GWAS-identified LMO1 gene polymorphisms and neuroblastoma risk in a Southern Chinese population. We genotyped the four polymorphisms in 256 neuroblastoma cases and 531 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. False-positive report probability was calculated for all significant findings. We found that the rs110419 A > G polymorphism was associated with a significantly decreased neuroblastoma risk (AG vs. AA: adjusted OR = 0.65, 95% CI = 0.47–0.91; GG vs. AA: adjusted OR = 0.58, 95% CI = 0.36–0.91; AG/GG vs. AA: adjusted OR = 0.63, 95% CI = 0.46–0.86), and the protective effect was more predominant in children of age > 18 months, males, subgroups with tumor in adrenal gland and mediastinum, and patients in clinical stages III/IV. These results suggested that LMO1 gene rs110419 A > G polymorphism may contribute to protection against neuroblastoma. Our findings call for further validation studies with larger sample size.
Highlights
Neuroblastoma is an embryonic cancer that arises from primordial cells during fetal or early childhood development [1]
While protective genotypes of the four single nucleotide polymorphisms (SNPs) were combined, we found the individuals with 4 protective genotypes experienced a significantly decreased neuroblastoma risk when compared with those with 0–3 protective genotypes (Adjusted Odds ratios (ORs) = 0.51, 95% confidence intervals (CIs) = 0.32–0.81, P = 0.004)
In the current case-control study with 256 neuroblastoma cases and 531 healthy controls, we verified that the LIM domain only 1 (LMO1) rs110419 A > G polymorphism was associated with a decreased neuroblastoma risk
Summary
Neuroblastoma is an embryonic cancer that arises from primordial cells during fetal or early childhood development [1]. It is the most commonly diagnosed extracranial solid tumor in childhood, accounting for more than 7% of malignancies in patients younger than 15 years [1, 2]. In the United States, the incidence rate of neuroblastoma is about 1 in 7000 live newborns [3], while the rate is roughly 7.7 per million in China [4]. 1% of the neuroblastoma patients have a family history and they are generally diagnosed at a much earlier age and more prone to develop multifocal primary tumors [5, 6]. Neuroblastoma has devastating impacts on affected family and is a great challenge for public health [10]
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