Department of Hematology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
Department of Clinical Laboratory, Biobank, Harbin Medical University Cancer Hospital, Harbin, China.
J Clin Lab Anal. 2019 Nov;33(9):e22988. doi: 10.1002/jcla.22988. Epub 2019 Jul 25.
Wilms tumor, derived from embryonic cells, accounts for a large proportion of pediatric renal tumors. MYCN encoded by MYCN proto-oncogene, a member of the MYC family, is a BHLH transcription factor. It plays a critical role in tumorigenesis and predicts poor clinical outcomes in various types of cancer. However, the role of MYCN remained unclarified in Wilms tumor. In this study, we investigated the association between MYCN gene polymorphisms and Wilms tumor susceptibility.
Four MYCN gene polymorphisms (rs57961569 G > A, rs9653226 T > C, rs13034994 A > G, and rs60226897 G > A) were genotyped in 183 cases and 603 controls. Adjusted odds ratios (AORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between MYCN gene polymorphisms and Wilms tumor susceptibility.
Overall, no significant association was found for any of the four MYCN gene polymorphisms. Interestingly, in the stratification analysis, the rs57961569 was found to be associated with decreased Wilms tumor susceptibility in the children older than 18 months (AOR = 0.65, 95% CI = 0.42-1.00, P = .050). Moreover, older children carrying 2-4 risk genotypes were at increased risk of Wilms tumor (OR = 1.55, 95% CI = 1.001-2.40, P = .0497). Haplotype GCAA was shown to significantly increased Wilms tumor risk (AOR = 2.40, 95% CI = 1.12-5.14, P = .024).
Our study demonstrated that these MYCN gene polymorphisms might be low penetrant variants in Wilms tumor.
Wilms 肿瘤来源于胚胎细胞，占儿童肾肿瘤的很大比例。MYCN 原癌基因编码的 MYCN 蛋白，是 MYC 家族的一个成员，是一个 BHLH 转录因子。它在肿瘤发生中起着关键作用，并预测各种癌症的不良临床结局。然而，MYCN 在 Wilms 肿瘤中的作用仍不清楚。在这项研究中，我们研究了 MYCN 基因多态性与 Wilms 肿瘤易感性之间的关系。
在 183 例病例和 603 例对照中，对 4 个 MYCN 基因多态性（rs57961569 G>A、rs9653226 T>C、rs13034994 A>G 和 rs60226897 G>A）进行了基因分型。采用调整后的比值比（AOR）和 95%置信区间（CI）来评估 MYCN 基因多态性与 Wilms 肿瘤易感性之间的关系。
总体而言，这四个 MYCN 基因多态性均无显著相关性。有趣的是，在分层分析中，rs57961569 与 18 个月以上儿童 Wilms 肿瘤易感性降低有关（AOR=0.65，95%CI=0.42-1.00，P=0.050）。此外，携带 2-4 个风险基因型的大龄儿童患 Wilms 肿瘤的风险增加（OR=1.55，95%CI=1.001-2.40，P=0.0497）。GCAA 单体型显著增加 Wilms 肿瘤风险（AOR=2.40，95%CI=1.12-5.14，P=0.024）。
我们的研究表明，这些 MYCN 基因多态性可能是 Wilms 肿瘤的低外显率变异。
