Association of m1A modification genes polymorphisms with glioma risk in Chinese children Running head: m1A genes polymorphisms and glioma risk

Abstract Background Glioma is a highly heterogeneous malignancy with a high mortality rate, poor prognosis. m1A is an RNA methylation modification that plays a vital role in determining cell fate and cell cycle regulation, and cancer development. However, whether single nucleotide polymorphisms (SNPs) of m1A modification genes are associated with glioma risk is unclear. Methods We recruited 314 pediatric glioma patients and 380 cancer-free controls from China and genotyped 20 SNPs of m1A modification genes TRMT10C, TRMT61B, TRMT6, TRM61, ALKBH1, YTHDC1, YTHDF1, and YTHDF2 by TaqMan method. The association of polymorphisms with glioma risk was assessed by the odds ratios (ORs) and 95% confidence intervals (CIs) generated by logistic regression models. Stratified analysis was performed by age, gender, tumor subtype, and clinical stage. Results The results showed that TRMT10C rs2303476, TRMT10C rs4257518, TRM61rs2296484, YTHDF2 rs3738067 polymorphisms, and carriage of 2-4 risk genotypes (rs7641261 CT/TT, rs2303476 TC/CC, rs4257518 GG, and rs3762735 GG) were significantly associated with increased risk of glioma, TRMT61Brs4563180, YTHDC1 rs2293595, YTHDC1 rs3813832 polymorphisms and carrying 1-3 protective genotypes (rs2293596 CC, rs2293595 TC/CC, and rs3813832 TC/ CC) were significantly associated with reduced risk of glioma. In addition, analysis of the expression quantitative trait locus showed that TRM61rs2296484 T genotype significantly increased TRM61 mRNA expression, YTHDF2rs3738067 G genotype significantly increased YTHDF2 mRNA expression, and TRMT61B rs4563180 C genotype significantly decreased TRMT61B mRNA expression. Conclusions Overall, we identified several promising candidates for m1A modification gene polymorphisms as biomarkers of glioma risk.