Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China.
Department of Pediatric Surgery, Hunan Children's Hospital, Changsha, Hunan, China.
J Gene Med. 2020 Nov;22(11):e3249. doi: 10.1002/jgm.3249. Epub 2020 Jul 21.
Hepatoblastoma is a commonly occurring embryonal tumors in children. N6-methyladenosine (m A) plays a critical role in gene expression, thus contributing to the occurrence and progression of cancer. RNA splicing is regulated by the nuclear m A reader YTHDC1, yet the roles of YTHDC1 polymorphisms in hepatoblastoma remain unclear.
We conducted a seven-center case-control study to determine the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C and rs3813832 T>C) and hepatoblastoma susceptibility. We recruited 313 hepatoblastoma patients and 1446 healthy controls.
There was no significant association between all of these polymorphisms and hepatoblastoma susceptibility in single locus or combined analysis. Stratification analysis revealed that rs2293596 TC/CC genotype carriers had a higher risk of developing hepatoblastoma in the subgroup of clinical stages III + IV [adjusted odds ratio (OR) = 1.80, 95% confidence interval (CI) = 1.18-2.76, p = 0.007]. In addition, 3 risk genotype carriers are more likely to develop hepatoblastoma in the subgroup of clinical stages III + IV (adjusted OR = 1.80, 95% CI = 1.18-2.76, p = 0.007). Furthermore, false-positive probability analysis was used to notarize our findings. Haplotype analysis indicated that there was no significant association between inferred haplotypes of YTHDC1 gene based on observed genotypes and hepatoblastoma risk.
In conclusion, our findings suggest that the rs2293596 T>C polymorphism may contribute to hepatoblastoma susceptibly and YTHDC1 gene polymorphisms may have a cumulative effect on hepatoblastoma risk.
肝母细胞瘤是儿童中常见的胚胎性肿瘤。N6-甲基腺苷(m A)在基因表达中发挥着关键作用,从而促进癌症的发生和发展。RNA 剪接受核 m A 阅读器 YTHDC1 调控,但 YTHDC1 多态性在肝母细胞瘤中的作用尚不清楚。
我们进行了一项七中心病例对照研究,以确定 YTHDC1 基因多态性(rs2293596 T>C、rs2293595 T>C 和 rs3813832 T>C)与肝母细胞瘤易感性之间的关系。我们招募了 313 名肝母细胞瘤患者和 1446 名健康对照者。
在单核苷酸或联合分析中,这些多态性与肝母细胞瘤易感性均无显著相关性。分层分析显示,rs2293596 TC/CC 基因型携带者在临床分期 III+IV 亚组中发生肝母细胞瘤的风险更高[校正比值比(OR)=1.80,95%置信区间(CI)=1.18-2.76,p=0.007]。此外,3 个风险基因型携带者在临床分期 III+IV 亚组中更有可能发生肝母细胞瘤(校正 OR=1.80,95%CI=1.18-2.76,p=0.007)。此外,还使用假阳性概率分析对我们的研究结果进行了公证。单体型分析表明,基于观察到的基因型推断的 YTHDC1 基因的推测单体型与肝母细胞瘤风险之间没有显著关联。
总之,我们的研究结果表明,rs2293596 T>C 多态性可能与肝母细胞瘤易感性有关,YTHDC1 基因多态性可能对肝母细胞瘤风险有累积作用。