Liu Yanfei, Zhu Jinhong, Wang Xianqiang, Zhang Wenli, Li Yong, Yang Zhonghua, Zhang Jiao, Cheng Jiwen, Li Li, Li Suhong, He Jing, Bian Jun
Department of Pathology, Xi'an Children's Hospital, Xi'an Jiaotong University Affiliated Children's Hospital, Xi'an 710003, Shaanxi, China.
Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin 150040, Heilongjiang, China.
J Cancer. 2024 Aug 19;15(16):5396-5402. doi: 10.7150/jca.98555. eCollection 2024.
N1-methyladenosine (mA) is a reversible epigenetic modification of RNAs. Aberrant mA modification levels due to dysregulation of mA regulators have been observed in multiple cancers. tRNA methyltransferase 10C (TRMT10C) can install mA in RNAs; however, its role in hepatoblastoma remains unknown. We conducted this study to identify causal polymorphisms in the gene for hepatoblastoma susceptibility in a cohort of Chinese children (313 cases vs. 1446 controls). The genotypes of four potential functional polymorphisms (rs7641261 C>T, rs2303476 T>C, rs4257518 A>G, and rs3762735 C>G) were determined in participants using TaqMan real-time PCR. The associations of these polymorphisms with hepatoblastoma susceptibility were estimated by logistic regression analysis adjusted for age and sex. All four polymorphisms were significantly associated with hepatoblastoma risk. In particular, under the recessive genetic model, these polymorphisms conferred an increased risk of hepatoblastoma: rs7641261 C>T [adjusted odds ratio (OR)=1.64, 95% confidence interval (CI)=1.04-2.58, =0.033], rs2303476 T>C (adjusted OR=1.87, 95% CI=1.16-3.02, =0.010), rs4257518 A>G (adjusted OR=1.45, 95% CI=1.09-1.94, =0.012), and rs3762735 C>G (adjusted OR=3.83, 95% CI=2.15-6.82, <0.0001). Combined analysis revealed that kids had an increased risk of developing hepatoblastoma if they harbored at least one risk genotype (adjusted OR=1.94, 95% CI=1.48-2.54, <0.0001). In addition, the combined risk effects of the four SNPs persisted across all the subgroups. We identified four hepatoblastoma susceptibility loci in the gene. Identifying more disease-causing loci may facilitate the development of genetic marker panels to predict individuals' hepatoblastoma predisposition.
N1-甲基腺苷（mA）是RNA的一种可逆表观遗传修饰。在多种癌症中，已观察到由于mA调节因子失调导致的异常mA修饰水平。tRNA甲基转移酶10C（TRMT10C）可在RNA中安装mA；然而，其在肝母细胞瘤中的作用尚不清楚。我们开展这项研究，以在中国儿童队列（313例病例对1446例对照）中确定肝母细胞瘤易感性基因中的因果多态性。使用TaqMan实时PCR确定了参与者中四个潜在功能多态性（rs7641261 C>T、rs2303476 T>C、rs4257518 A>G和rs3762735 C>G）的基因型。通过对年龄和性别进行调整的逻辑回归分析，估计这些多态性与肝母细胞瘤易感性的关联。所有四个多态性均与肝母细胞瘤风险显著相关。特别是，在隐性遗传模型下，这些多态性增加了肝母细胞瘤的风险：rs7641261 C>T [调整后的优势比（OR）=1.64，95%置信区间（CI）=1.04 - 2.58，P = 0.033]，rs2303476 T>C（调整后的OR = 1.87，95% CI = 1.16 - 3.02，P = 0.010），rs4257518 A>G（调整后的OR = 1.45，95% CI = 1.09 - 1.94，P = 0.012），以及rs3762735 C>G（调整后的OR = 3.83，95% CI = 2.15 - 6.82，P < 0.0001）。联合分析显示，如果儿童携带至少一种风险基因型，则患肝母细胞瘤的风险增加（调整后的OR = 1.94，95% CI = 1.48 - 2.54，P < 0.0001）。此外，四个单核苷酸多态性的联合风险效应在所有亚组中均持续存在。我们在该基因中确定了四个肝母细胞瘤易感位点。识别更多致病位点可能有助于开发遗传标记面板，以预测个体的肝母细胞瘤易感性。
