ALKBH1 gene polymorphisms confer hepatoblastoma susceptibility in Chinese children

Hepatoblastoma is the most common malignant liver tumor of embryonic origin in children; however, its underlying etiology remains unclear. N1-methyladenosine (m1A) modification is widely found in various human tissues and has been demonstrated to regulate tumorigenesis, but no studies have explored the role of ALKBH1 in the development of hepatoblastoma. We genotyped three ALKBH1 gene polymorphisms (rs1048147 C > A, rs6494 T > A, and rs176942 A > G) via the TaqMan method for 313 patients with hepatoblastoma and 1446 healthy subjects, after which the odds ratios (ORs), 95% confidence intervals (CIs), and P values for each polymorphism were calculated. We found that all the three polymorphisms were significantly associated with hepatoblastoma susceptibility. The rs1048147 C > A was shown to reduce hepatoblastoma risk (adjusted OR = 0.72, 95% CI = 0.56–0.92, P = 0.009) under dominant model, whereas rs6494 T > A (adjusted OR = 6.17, 95% CI = 1.37–27.37, P = 0.018) and rs176942 A > G (adjusted OR = 2.12, 95% CI = 1.22–3.69, P = 0.008) significantly increased hepatoblastoma risk under recessive model. Stratified analysis indicated that the rs1048147 CA/AA genotype decreased hepatoblastoma risk in children aged ≥ 17 months, females, and those with clinical stages I + II, whereas the rs176942 GG genotype increased the risk of hepatoblastoma in females. In addition, carriers of 2–3 risk genotypes had higher risk of tumor development, specifically among children aged ≥ 17 months, males, and those diagnosed with clinical stages I–II disease. Finally, eQTL analysis revealed that the three polymorphisms were associated with the expression levels of ADCK1, SNW1, and SLIRP. Overall, our findings revealed a significant association between ALKBH1 gene polymorphisms and hepatoblastoma susceptibility.