ALKBH1 Gene rs6494 T>A Polymorphism Decreases Wilms Tumour Risk in Chinese Children

Wilms tumour (WT) is the most predominant renal carcinoma that affects children, and the understanding of the genetic mechanisms underlying WT development is continually evolving. The role of the demethylase ALKBH1, which is known for its association with diverse cancers, in WT has never been explored. Here, we aimed to investigate the associations between genetic variants of ALKBH1 and WT risk in Chinese children. A total of 414 WT patients and 1199 healthy controls were recruited from five centres in China. Three polymorphisms (rs1048147, rs6494 and rs176942) of the ALKBH1 gene were genotyped via the TaqMan genotyping assay. We found that rs6494 T>A was significantly associated with a reduced risk of WT [TA vs. TT: adjusted odds ratio (AOR) = 0.59, 95% confidence interval (CI) = 0.39-0.87, p = 0.009; TA/AA vs. TT: AOR = 0.61, 95% CI = 0.42-0.91, p = 0.014]. Stratification analysis revealed that the protective genotype of rs6494 (TA/AA) was significantly associated with reduced WT risk in subgroups with ages younger than 18 months, male sex and clinical stages III and III-IV. Moreover, through eQTL analysis, we observed that rs6494 T>A was associated with reduced ALKBH1 expression and elevated SNW1 and ADCK1 expression. We identified the rs6494 T>A polymorphism of the ALKBH1 gene as a WT susceptibility locus, providing valuable insights into the etiology underlying WT susceptibility.