H19 基因多态性与中国儿童肾母细胞瘤发病风险的四中心病例对照研究
H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four-center case-control study.
机构信息
Department of Pediatric Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
出版信息
Mol Genet Genomic Med. 2021 Feb;9(2):e1584. doi: 10.1002/mgg3.1584. Epub 2021 Jan 5.
BACKGROUND
Wilms tumor is the most common pediatric renal cancer. However, genetic bases behind Wilms tumor remain largely unknown. H19 is a critical maternally imprinted gene. Previous studies indicated that single nucleotide polymorphisms (SNPs) in the H19 can modify the risk of several human malignancies. Epigenetic errors at the H19 locus lead to biallelic silencing in Wilms tumors. Genetic variations in the H19 may be related to Wilms tumor susceptibility.
METHODS
We conducted a four-center study to investigate whether H19 SNP was a predisposing factor to Wilms tumor. Three polymorphisms in the H19 (rs2839698 G > A, rs3024270 C > G, rs217727 G > A) were genotyped in 355 cases and 1070 cancer-free controls, using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations.
RESULTS
We found that all of these three polymorphisms were significantly associated with Wilms tumor risk alterations. The rs2839698 G > A polymorphism (AG vs. GG: adjusted OR = 0.74, 95% CI = 0.57-0.96, p = 0.024; AA vs. GG: adjusted OR = 1.52, 95% CI = 1.05-2.22, p = 0.027), the rs3024270 C > G polymorphism (CG vs. CC: adjusted OR = 0.61, 95% CI = 0.46-0.81, p = 0.0007; and the rs217727 polymorphism (AG vs. GG: adjusted OR = 0.76, 95% CI = 0.58-0.99, p = 0.035). The Carriers of 1, 2, and 1-2 risk genotypes were inclined to develop Wilms tumor compared with those without risk genotype (adjusted OR = 1.36, 95% CI = 1.02-1.80, p = 0.037; adjusted OR = 1.84, 95% CI = 1.27-2.67, p = 0.001; adjusted OR = 1.50, 95% CI = 1.17-1.92, p = 0.002, respectively). The stratified analysis further revealed that rs2839698 AA, rs217727 AA, and 1-2 risk genotypes could strongly increase Wilms tumor risk among children above 18 months of age, males, and with clinical stage I+II disease.
CONCLUSION
Our findings indicate that genetic variations in the H19 may confer Wilms tumor risk.
背景
肾母细胞瘤是儿童中最常见的肾恶性肿瘤。然而，肾母细胞瘤的遗传基础仍很大程度上未知。H19 是一个关键的母系印记基因。先前的研究表明，H19 中的单核苷酸多态性（SNP）可以改变几种人类恶性肿瘤的风险。H19 位点的表观遗传错误导致肾母细胞瘤中双等位基因沉默。H19 中的遗传变异可能与肾母细胞瘤易感性有关。
方法
我们进行了一项四中心研究，以调查 H19 SNP 是否是肾母细胞瘤的易感因素。使用 Taqman 方法，在 355 例病例和 1070 例无癌症对照中，对 H19 中的三个 SNP（rs2839698 G > A、rs3024270 C > G、rs217727 G > A）进行了基因分型。使用比值比（OR）和 95%置信区间（CI）来评估关联的强度。
结果
我们发现这三个多态性均与肾母细胞瘤风险改变显著相关。rs2839698 G > A 多态性（AG 与 GG：调整 OR = 0.74，95%CI = 0.57-0.96，p = 0.024；AA 与 GG：调整 OR = 1.52，95%CI = 1.05-2.22，p = 0.027）、rs3024270 C > G 多态性（CG 与 CC：调整 OR = 0.61，95%CI = 0.46-0.81，p = 0.0007；rs217727 多态性（AG 与 GG：调整 OR = 0.76，95%CI = 0.58-0.99，p = 0.035）。与无风险基因型相比，携带 1、2 和 1-2 个风险基因型的个体更倾向于发生肾母细胞瘤（调整 OR = 1.36，95%CI = 1.02-1.80，p = 0.037；调整 OR = 1.84，95%CI = 1.27-2.67，p = 0.001；调整 OR = 1.50，95%CI = 1.17-1.92，p = 0.002，分别）。分层分析进一步表明，rs2839698 AA、rs217727 AA 和 1-2 个风险基因型可强烈增加 18 个月以上儿童、男性和临床分期 I+II 疾病中肾母细胞瘤的风险。
结论
我们的研究结果表明，H19 中的遗传变异可能会导致肾母细胞瘤的风险增加。
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