Hepatoblastoma is a form of cancer that accounts for 80% of childhood liver cancers, but only 1% of childhood cancers in total. It usually presents between birth and three years of age. As it is a relatively rare tumour type, there have been few opportunities to study it and consequently little is known about its origins and drivers. That said, methyltransferases targeting mRNA have been implicated in hepatoblastoma. The Wilms tumor 1-associated protein (WTAP) is thought to play a key role in methyltransferase complex formation, but its role in hepatoblastoma is not well studied.
Jing He of Guangzhou Medical University, China, and colleagues, conducted a multi-center case-control study to investigate the association between functional single nucleotide polymorphisms (SNPs) in the WTAP gene and hepatoblastoma risk in children of Chinese ancestry. The results were published in the journal Molecular Therapy Oncolytics.
There were 313 hepatoblastoma cases and 1,446 cancer-free controls. The WTAP rs7766006 T allele was significantly associated with decreased hepatoblastoma risk. The rs1853259 GG genotype was associated with hepatoblastoma risk in children under 17 months of age.
People with the rs7766006 T genotype, which is protective, had a significantly higher level of WTAP mRNA in their liver, according to the Genotype-Tissue Expression (GTEx) database. Cell cultured fibroblasts also produced more WTAP if they had the rs7766006 T genotype.
Increased WTAP is associated with hepatoblastoma. Exactly why the rs7766006 T genotype reduces risk in the background of elevated WTAP levels is unclear. One possibility is that it has negative functional consequences for WTAP. A limitation of the study was that the authors did not attempt to address this question.
In summary, our study has illustrated the contributions of WTAP gene SNPs to hepatoblastoma risk. To be noted, this is the first multicenter evaluation of the association between WTAP gene SNPs and hepatoblastoma susceptibility. Our study underscores the role of WTAP gene SNPs in the development of hepatoblastoma. The association of these loci to hepatoblastoma suggests potential biological mechanisms worthy of further investigation.