Zhang Wenli, Zhu Jinhong, Bian Jun, Zhou Chunlei, Zhang Shouhua, He Shaohua, Lu Hongting, Wang Yizhen, He Jing
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, 9 Jinsui Road, Guangzhou, 510623, Guangdong, China.
Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin, 150040, Heilongjiang, China.
BMC Med Genomics. 2025 Jul 1;18(1):105. doi: 10.1186/s12920-025-02179-4.
Hepatoblastoma is the most prevalent liver cancer affecting children, and its intricate causes are closely linked to genetic variations. This study interrogated the influence of the miR-34b/c rs4938723 T > C polymorphism in hepatoblastoma predisposition in a Han Chinese children study population, comprising 193 cases and 773 controls from East China.
Genotyping was performed via the TaqMan technique. The association between this genetic variant and hepatoblastoma susceptibility was determined via logistic regression models adjusted for age and sex.
Our results show that the TC genotype of the miR-34b/c rs4938723 polymorphism is associated with a significantly reduced risk of hepatoblastoma under a heterozygous model (adjusted OR = 0.59, 95% CI = 0.41-0.84, P = 0.003), whereas the CC genotype is associated with an increased risk under a recessive model (adjusted OR = 1.79, 95% CI = 1.17-2.73, P = 0.008). Further stratified analysis revealed that the TC/CC genotypes were linked to a lower risk of hepatoblastoma in girls and those with advanced clinical stages (III + IV). Furthermore, we identified the miR-34b/c rs4938723 polymorphism as an expression quantitative trait locus that affects the expression of nearby genes. The CC genotype was related to a decrease in LAYN expression in the colon, brain, and lung and decreased PPP2R1B expression in the testis. These findings suggest that miR-34b/c rs4938723 T > C has the potential to modify hepatoblastoma predisposition through its regulatory effects on gene expression.
This study provides evidence for the association between the miR-34b/c rs4938723 polymorphism and hepatoblastoma risk in Chinese Han children from East China, suggesting that this polymorphism may have potential as a biomarker for predicting hepatoblastoma susceptibility in this specific population.
肝母细胞瘤是影响儿童的最常见的肝癌,其复杂病因与基因变异密切相关。本研究在一个由193例病例和来自中国东部的773名对照组成的汉族儿童研究人群中,探讨了miR - 34b/c rs4938723 T>C多态性对肝母细胞瘤易感性的影响。
通过TaqMan技术进行基因分型。通过对年龄和性别进行调整的逻辑回归模型确定该基因变异与肝母细胞瘤易感性之间的关联。
我们的结果表明,在杂合子模型下,miR - 34b/c rs4938723多态性的TC基因型与肝母细胞瘤风险显著降低相关(调整后的OR = 0.59,95%CI = 0.41 - 0.84,P = 0.003),而在隐性模型下,CC基因型与风险增加相关(调整后的OR = 1.79,95%CI = 1.17 - 2.73,P = 0.008)。进一步的分层分析显示,TC/CC基因型与女孩及临床晚期(III + IV期)的肝母细胞瘤风险较低有关。此外,我们确定miR - 34b/c rs4938723多态性为一个影响附近基因表达的表达数量性状位点。CC基因型与结肠、脑和肺中LAYN表达降低以及睾丸中PPP2R1B表达降低有关。这些发现表明,miR - 34b/c rs4938723 T>C有可能通过其对基因表达的调控作用来改变肝母细胞瘤易感性。
本研究为华东地区中国汉族儿童中miR - 34b/c rs4938723多态性与肝母细胞瘤风险之间的关联提供了证据,表明该多态性可能有潜力作为预测这一特定人群肝母细胞瘤易感性的生物标志物。