Yang Zhonghua, Deng Yuyao, Zhang Keren, Bai Yuzuo, Zhu Jinhong, Zhang Jiao, Xin Yijuan, Li Li, He Jing, Wang Weilin
Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China.
Department of Clinical Medicine, The Fourth Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning, China.
J Cancer. 2020 Mar 15;11(12):3512-3518. doi: 10.7150/jca.42798. eCollection 2020.
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 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, =0.0006; AA vs. CA/CC: adjusted OR=2.11, 95% CI=1.43-3.12, =0.0002) and rs9404590 T>G (GG vs. TT: adjusted OR=1.89, 95% CI=1.20-3.00, =0.007; GG vs. TT/TG: adjusted OR=1.87, 95% CI=1.20-2.92, =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 gene expression. We further validated our findings using false-positive probability analysis. This finding suggested that gene polymorphisms may be associated with an increased predisposition to hepatoblastoma.
肝母细胞瘤是儿童期的恶性肝脏肿瘤之一。然而，肝母细胞瘤发生的遗传机制在很大程度上仍不清楚。先前的研究表明，lin-28同源物B（LIN28B）可能在肝母细胞瘤的发生发展中起作用。为了检测中国儿童基因多态性与肝母细胞瘤风险之间的关联，我们进行了一项五中心病例对照研究，纳入275例肝母细胞瘤患者和1018例无癌对照。使用Taqman方法对4个潜在的功能性多态性进行基因分型。采用优势比（OR）和95%置信区间（CI）来评估关联强度。我们发现，rs314276 C>A多态性（AA与CC相比：校正OR=2.05，95%CI=1.36-3.10，P=0.0006；AA与CA/CC相比：校正OR=2.11，95%CI=1.43-3.12，P=0.0002）和rs9404590 T>G（GG与TT相比：校正OR=1.89，95%CI=1.20-3.00，P=0.007；GG与TT/TG相比：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。风险基因型的联合分析表明，具有4种风险基因型的患者比携带1至3种风险基因型的患者发生肝母细胞瘤的几率更高。分层分析显示，rs314276 AA基因型与各年龄和性别组以及临床III+IV期病例的肝母细胞瘤风险之间存在显著关联。rs9404590 GG基因型与年龄≥17个月的参与者、女性以及临床III+IV期疾病患者的肝母细胞瘤风险相关。此外，4种风险基因型在各年龄和性别组以及临床III+IV期疾病组中均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，rs9404590 T>G多态性与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，基因多态性可能与肝母细胞瘤易感性增加有关。
