Correlation Of Genetic Variation Of FAT10Gene To Development Of Hepatocellular Carcinoma

Objectives: This study examined whether single nucleotide polymorphism inexonic and flanking sequence of the human HLA-F adjacent transcript10(FAT10)gene were associated with susceptibility and clinicopathological development ofhapatocellular carcinoma (HCC).Methods: A total of522subjects, including268healthy controls and254patients with HCC, were recruited. Genotyping was done by using DNA sequencing.Haplotypes and Linkage disequilibrium analysis were estimated by haploviewsoftware.The odds ratios (ORs) and95%confidence intervals (CIs) were calculatedusing unconditional logistic regression model to estimate the correlations of theFAT10genetic variation to development of hepatocellular carcinoma.Results: Ten SNPs in FAT10were identifed in both HCC patients and controlsubjects. The-143A/G,+3476T/C,+3527T/C tagSNPs that were selected forassociation and haplotype analysis were chosen based on the data of DNA sequencingand linkage disequilibrium analysis. The-143A/G,+3476T/C genotypes wereassociated with a decreased risk for HCC (OR=0.38,95%CI:0.22-0.66and OR=0.34,95%CI:0.21-0.56, p<0.05), but No SNPs were associated with diseaseclinicopathology (all p-values>0.05). Furthermore, a total of4haplotypes were found,namely ATT, ATC, GCT, ACT. the frequency of GCT and ACT haplotypes wassignificantly lower for HCC patients than for control subjects (OR=0.41,95%CI=0.24-0.70and OR=0.43,95%CI=0.22-0.98, both p<0.05) and the frequencyof ATT was significantly higher for HCC patients than for control subjects (OR=1.64,95%CI=1.24-2.17, p<0.05).10-million permutation testing also indicated that the ATTand GCT haplotypes were associated with HCC susceptibility. The patients carryingATT were in higher tumor and Clinical stage (p<0.05), while the patients carryingGCT were in lower tumor and Clinical stage (p <0.05)Conclusion: The genetic variation in exonic and flanking sequence of FTA10gene may be involved in the susceptibility and clinicopathological development of HCC, the ATT might serve as genetic marker for HCC．...