Genetic Variation in the Fat10 Gene is Associated with Risk of Hepatocellular Carcinoma in a Chinese Population

Background and
Objectives: This study examined whether variation in exonic and flanking sequences of the human HLA-F adjacent transcript 10 (FAT10) gene might be associated with susceptibility and clinicopathological development of hapatocellular carcinoma (HCC).
Methods: A total of 522 subjects, including 268 healthy controls and 254 patients with HCC, were recruited. Genotyping was accomplished using DNA sequencing. Haplotypes were determined through genotypic and disequilibrium analysis of identified single nucleotide polymorphisms (SNPs).
Results: Ten SNPs in FAT10 were identified, namely -143 A/G (rs362535), -121 A/G (rs2272991), +3446 C/T, +3476 T/C (rs2076484), +3527 T/C (rs2076485), +3607 T/C (rs2076486), +3620 C/G (rs2076487), +3803 C/G (rs8337), +3809 G/T (rs7757931), +3833 G/C (rs444013). +3446 C/T is a novle polymorphism. The -143 A/G, -121 A/G, +3476 T/C, +3607 T/C, +3620 C/G and +3809 G/T genotypes were associated with a decreased risk for HCC (all P-values <0.05). No SNPs were associated with disease clinicopathology (all P-values > 0.05). Furthermore, under the analysis of haplotype, GGCTCGT and AGCTCGT were related to reduced HCC risk (OR=0.41, 95%CI=0.24, 0.70, P<0.05 and OR=0.43, 95% CI=0.22, 0.983, P<0.05, respectively), while AATTTCG was associated with an increased risk (OR= 1.64, 95% CI=1.24-2.17, P<0.05). 10-million permutation testing also indicated the AATTTCG and GGCTCGT haplotypes to be associated with HCC susceptibility (both P-values <0.05). Patients carrying AATTTCG were in higher tumor and clinical stages (P<0.05), while GGCTCGT appeared protective in this context (P <0.05).
Conclusion: This study provides first evidence that FAT10 gene genetic variants may be involved in the susceptibility and clinicopathological development of HCC in the Chinese han population.