TRMT6 gene rs236110 C > A polymorphism increases the risk of Wilms tumor

Abstract

tRNA methyltransferase 6 (TRMT6)is an enzyme catalyzing N1-methyladenosine, a reversible modification in RNA, including tRNA, mRNA, rRNA, and lncRNA. Increasing evidence has shown the implications of this post-transcriptional modification and its regulators in carcinogenesis. However, its roles in Wilms tumor haven't been reported. In this study, four TRMT6 gene polymorphisms (rs236170 A > G, rs451571 T > C, rs236188 G > A, and rs236110 C > A) were tested for association with susceptibility to Wilms tumor, the most frequently diagnosed pediatric renal tumor. TaqMan method was adopted to analyze the genotypes of these polymorphisms in 414 cases and 1199 controls. Among the four TRMT6 gene polymorphisms, only the rs236110 C > A displayed a significant association with the risk of Wilms tumor [AA vs. CC, adjusted odds ratio (OR) = 1.93, 95 % confidence interval (CI) = 1.14-3.27, P = 0.015]. This association was confirmed under the recessive models (AA vs. CC/CA, OR = 1.92, 95 % CI = 1.14-3.23, P = 0.015). Furthermore, after stratifying by age, gender, and clinical stage, we mainly detected significant associations for the rs236110 C > A in children older than 18 months, boys, and those with stage IV or III + IV diseases. The rs236110 A allele was significantly associated with decreased expression of MCM8. In conclusion, we identified the rs236110 C > A in the TRMT6 gene as a Wilms tumor susceptibility locus, and this polymorphism warrants more validation studies to be translated into individualized risk prediction strategies for children.

Keywords: Polymorphism; Susceptibility; TRMT6; Wilms tumor; m1A modification.