Genetic Variations in Base Excision Repair Pathway Genes and Risk of Hepatoblastoma: a Seven-center Case-control Study

Hepatoblastoma is a rare childhood liver cancer without known explicit etiology. Base excision repair (BER) pathway genes have been implicated in the pathophysiology of cancer, yet the role of BER pathway gene single nucleotide polymorphisms (SNPs) on hepatoblastoma risk still awaits to be explored. This study aims to determine whether hepatoblastoma risk be modulated by polymorphisms in the BER pathway genes based on genotyped data from 313 cases and 1446 controls. We applied TaqMan assay to genotype these included samples. We comprehensively genotyped 20 SNPs across six genes of BER, and estimated odds ratio (ORs), 95% confidence intervals (CIs), and -values of the selected SNPs' contribution to the risk of hepatoblastoma using logistic regression models. Only SNP rs293795 in the gene could significantly enhance hepatoblastoma risk under recessive model (adjusted OR=3.78, 95% CI=1.01-14.17, =0.047). Stratified analysis revealed that rs159153 TC/CC genotype decreased hepatoblastoma risk in male subgroup. Moreover, rs293795 GG and 1-3 risk genotypes could increase hepatoblastoma risk in clinical stages I+II and male subgroups, respectively. False-positive report probability validated the reliability of the significant results. Our findings provide some clues of a potential risk effect of BER pathway gene SNPs on hepatoblastoma. Further investigation is warranted to confirm these findings and to better elucidate the biological pathways involved.