MiR-196a2 rs11614913 C Allele is Associated with Increased Wilms Tumor Susceptibility in Chinese Children.
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Wilms tumor, also known as nephroblastoma, is the most common kidney cancer in children. The miR-196a2 rs11614913 T>C polymorphism has been identified as a susceptibility locus in various adult cancers. However, it is unclear whether this polymorphism also increases the risk of pediatric cancer. In this study, we examined the genotypes of miR-196a2 rs11614913 T>C in 416 pediatric patients with Wilms tumor and 936 age- and gender-matched healthy controls of Chinese Han ethnicity using the TaqMan technology. The association between rs11614913 T>C polymorphism and the susceptibility to Wilms tumor was analyzed by univariable and multivariable logistic regression analyses, and the odds ratio (OR) and 95% confidence interval (CI) were calculated. Overall analysis indicated that the miR-196a2 rs11614913 T>C was associated with an increased risk of Wilms tumor in the homozygous (adjusted OR (AOR)=1.58, 95% CI=1.14-2.21, P=0.007), additive (AOR=1.26, 95% CI=1.06-1.49, P=0.007), dominant (AOR=1.33, 95% CI=1.02-1.74, P=0.034), and recessive (AOR=1.38, 95% CI=1.05-1.81, P=0.023) models. Stratification analysis further demonstrated that the association was dependent on age and tumor stages rather than gender. Furthermore, miR-196a2 rs11614913 T>C was significantly associated with the disease risk only in children older than 18 months and those with III+IV stage tumors. The expression quantitative trait locus (eQTL) analysis showed that rs11614913 T>C was associated with decreased expression of HOXC-AS1 and increased expression of GPR84 and HOXC8. Our results provide evidence that miR-196a2 rs11614913 T>C may confer genetic susceptibility to Wilms tumor. These findings warrant validation in larger cohorts and across different ethnicities.