Potentially functional polymorphisms in the LIN28B gene contribute to neuroblastoma susceptibility in Chinese children.
Potentially functional polymorphisms in the LIN28B gene contribute to neuroblastoma susceptibility in Chinese children.
复制标题
DOI：
10.1111/jcmm.12846
复制
发表时间：
2016-08
影响因子：
5.3
通讯作者：
Xia H
中科院分区：
文献类型：
--
作者：
He J;Yang T;Zhang R;Zhu J;Wang F;Zou Y;Xia H
神经母细胞瘤是儿童中枢神经系统外最常见的实体瘤。然而，神经母细胞瘤的遗传因素仍然很大程度上不清楚。先前的全基因组关联研究表明，lin-28同源物B（LIN 28 B）可能在神经母细胞瘤的发展中起重要作用，也导致其总体生存率低。为了评估LIN 28 B基因多态性与中国南方人群神经母细胞瘤易感性之间的关系，我们对256例神经母细胞瘤病例和531例非癌症对照进行了这项研究。采用Taqman方法对4个潜在的功能多态性位点（rs 221634 A>T、rs 221635 T>C、rs314276 C>A和rs 9404590 T>G）进行基因分型。计算比值比（OR）和95%置信区间（CI），以评估所选单核苷酸多态性（SNP）与神经母细胞瘤易感性之间的关联。我们还进行了基因型-表型关联分析，以探索所选SNP对LIN 28 B基因转录本的影响。我们的研究结果表明，rs 221634 TT基因型与神经母细胞瘤风险增加相关（TT与AA/AT：调整OR = 1.50，95%CI = 1.04-2.17）。这种关联在男性、纵隔肿瘤患者以及早期临床阶段的患者中更为明显。此外，总体分析和分层分析也显示，携带2-4个风险基因型的神经母细胞瘤的风险增加。总之，这些结果表明LIN 28 B rs 221634 A>T多态性与中国南方儿童神经母细胞瘤风险增加相关。这些发现需要在涉及不同种族的大型研究中进一步验证。
Neuroblastoma is the most commonly diagnosed solid tumour outside the central nervous system in children. However, genetic factors underlying neuroblastoma remain largely unclear. Previous genome‐wide association study indicated that lin‐28 homolog B (LIN28B) might play an important role in the development of neuroblastoma and also contributed to its poor overall survival. With the purpose to evaluate the association between LIN28B gene polymorphisms and neuroblastoma susceptibility in Southern Chinese population, we conducted this study with 256 neuroblastoma cases and 531 cancer‐free controls. Four potentially functional polymorphisms (rs221634 A>T, rs221635 T>C, rs314276 C>A and rs9404590 T>G) were genotyped using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the associations between the selected single nucleotide polymorphisms (SNPs) and neuroblastoma susceptibility. We also performed genotype‐phenotype association analysis to explore the effects of the selected SNPs on LIN28B gene transcripts. Our results indicated that the rs221634 TT genotype was associated with an increased neuroblastoma risk (TT versus AA/AT: adjusted OR = 1.50, 95% CI = 1.04–2.17). The association was more pronounced in males, patients with tumour of mediastinum origin, as well as patients in early clinical stages. Moreover, overall analysis and stratified analysis also showed an increased risk of neuroblastoma for carrier of the 2–4 risk genotypes. In summary, these results indicated that the LIN28B rs221634 A>T polymorphism was associated with an increased neuroblastoma risk in Southern Chinese children. These findings need further validation in large studies with different ethnicities involved.