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, China.
School of Chinese Medicine, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China.
J Cell Mol Med. 2019 Oct;23(10):7105-7110. doi: 10.1111/jcmm.14561. Epub 2019 Jul 23.
Wilms tumour is a renal malignancy that commonly occurs in children. LIN28A gene overexpression has been reported to be involved in various human malignancies, while its roles in Wilms tumour risk are still under investigation. Here, we genotyped four LIN28A polymorphisms in 355 Wilms tumour patients and 1070 healthy controls from four hospitals in China. The genotyped single nucleotide polymorphisms (SNPs) include the following: rs3811464 G>A, rs3811463 T>C, rs34787247 G>A and rs11247957 G>A. Overall, we found that rs3811463 T>C and rs34787247 G>A were associated with increased risk of Wilms tumour. Combination analysis of risk genotypes showed that, compared to non-carriers, subjects with 1 risk genotype and 1-3 risk genotypes were more likely to develop Wilms tumour, with an adjusted odds ratio (OR) of 1.58 and 1.56, respectively. Stratified analysis further demonstrated that the risk effect remained prominent in some subgroups. We also found that presence of 1-3 risk genotypes was associated with Wilms tumour risk in subgroups > 18 months of age, females, males and those with clinical stage I + II diseases. Furthermore, expression quantitative trait locus (eQTL) analysis indicated that rs3811463 C allele was significantly associated with increased transcripts of LIN28A gene. These findings suggest that LIN28A gene polymorphisms may be associated with increased predisposition to Wilms tumour.
威尔姆斯瘤是一种常见于儿童的肾恶性肿瘤。已有报道称 LIN28A 基因过表达与多种人类恶性肿瘤有关，但其在威尔姆斯瘤风险中的作用仍在研究中。在这里，我们对来自中国 4 家医院的 355 名威尔姆斯瘤患者和 1070 名健康对照者的 4 个 LIN28A 多态性进行了基因分型。所鉴定的单核苷酸多态性（SNP）包括以下：rs3811464 G>A、rs3811463 T>C、rs34787247 G>A 和 rs11247957 G>A。总的来说，我们发现 rs3811463 T>C 和 rs34787247 G>A 与威尔姆斯瘤风险增加相关。风险基因型的组合分析表明，与非携带者相比，携带 1 个风险基因型和 1-3 个风险基因型的个体发生威尔姆斯瘤的风险更高，调整后的比值比（OR）分别为 1.58 和 1.56。分层分析进一步表明，这种风险效应在一些亚组中仍然显著。我们还发现，在年龄>18 个月、女性、男性和临床分期 I+II 疾病的亚组中，存在 1-3 个风险基因型与威尔姆斯瘤风险相关。此外，表达数量性状基因座（eQTL）分析表明，rs3811463 C 等位基因与 LIN28A 基因转录本的增加显著相关。这些发现表明 LIN28A 基因多态性可能与增加威尔姆斯瘤易感性有关。
