LIN28B gene polymorphisms modify hepatoblastoma susceptibility in Chinese children
LIN28B gene polymorphisms modify hepatoblastoma susceptibility in Chinese children
复制标题
LIN28B基因多态性改变中国儿童肝母细胞瘤易感性
DOI：
10.7150/jca.42798
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Wang, Weilin
中科院分区：
文献类型：
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作者：
Yang, Zhonghua;Deng, Yuyao;Wang, Weilin
肝母细胞瘤是儿童肝脏恶性肿瘤之一。然而，肝母细胞瘤发生的遗传机制仍不清楚。以往的研究表明lin-28同源物B（LIN 28 B）可能在肝母细胞瘤的发生发展中起作用。为了检测LIN 28 B基因多态性与中国儿童肝母细胞瘤风险之间的关系，我们对275例肝母细胞瘤患者和1018例非癌症对照进行了一项五中心病例对照研究。四个潜在的功能多态性基因分型使用Taqman方法。比值比（OR）和95%置信区间（CI）用于评估关联的强度。我们发现rs314276 C>A多态性（AA vs. CC：校正OR=2.05，95%CI =1.36-3.10，P=0.0006; AA vs. CA/CC：校正OR=2.11，95%CI =1.43-3.12，P=0.0002）和rs 9404590 T>G（GG vs. TT：校正OR=1.89，95% CI=1.20-3.00，P=0.007; GG vs. TT/TG：校正OR=1.87，95% CI=1.20-2.92，P=0.006）与肝母细胞瘤风险增加相关。风险基因型组合分析显示，具有4种风险基因型的患者发生肝母细胞瘤的机会高于1 ~ 3种风险基因型的携带者。分层分析显示rs314276 AA基因型与肝母细胞瘤风险在年龄和性别组以及临床分期III+IV病例中均存在显著相关性。rs 9404590 GG基因型与年龄≥17个月、女性和临床III+IV期患者的肝母细胞瘤风险相关。此外，四种风险基因型在年龄和性别组以及临床III+IV期疾病组中赋予更高的肝母细胞瘤易感性。基于基因型的基因表达分析证实，rs 9404590 T>G多态性与LIN 28 B基因表达改变显著相关。我们使用假阳性概率分析进一步验证了我们的发现。这一发现表明LIN 28 B基因多态性可能与肝母细胞瘤易感性增加有关。
Hepatoblastoma is one of the malignant liver tumors in children. However, genetic mechanisms underpinning the initiation of hepatoblastoma remain largely unclear. The previous study showed that lin-28 homolog B (LIN28B) might play a role in the development of hepatoblastoma. To detect the association between LIN28B gene polymorphisms and hepatoblastoma risk in Chinese children, we conducted a five-center case-control study of 275 hepatoblastoma patients and 1018 cancer-free controls. Four potentially functional polymorphisms were genotyped using the Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the strength of the associations. We found that the rs314276 C>A polymorphism (AA vs. CC: adjusted OR=2.05, 95% CI=1.36-3.10, P=0.0006; AA vs. CA/CC: adjusted OR=2.11, 95% CI=1.43-3.12, P=0.0002) and rs9404590 T>G (GG vs. TT: adjusted OR=1.89, 95% CI=1.20-3.00, P=0.007; GG vs. TT/TG: adjusted OR=1.87, 95% CI=1.20-2.92, P=0.006) were associated with increased hepatoblastoma risk. Combination analysis of risk genotypes showed that patients with four risk genotypes had a higher chance of developing hepatoblastoma than carriers of 1 to 3 risk genotypes. Stratification analysis showed the significant association between the rs314276 AA genotype and hepatoblastoma risk in both age and sex groups, as well as clinical stages III+IV cases. The rs9404590 GG genotype was associated with hepatoblastoma risk in participants' ≥17 months, in females, and for those with clinical stages III+IV disease. Furthermore, four risk genotypes confer higher hepatoblastoma susceptibility in both age and sex groups, as well as groups with clinical stages III+IV disease. Genotype-based gene expression analysis confirmed that the rs9404590 T>G polymorphism was significantly associated with altered LIN28B gene expression. We further validated our findings using false-positive probability analysis. This finding suggested that LIN28B gene polymorphisms may be associated with an increased predisposition to hepatoblastoma.