Abstract
Human leukocyte antigen (HLA)-DQB1 genetic polymorphisms are associated with an increased risk of hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC). We aimed to evaluate the influence of genetic polymorphisms in HLA-DQB1 exon region and neighboring single nucleotide polymorphisms (SNPs rs9275572 and rs2244546) on survival of HBV-related HCC patients undergoing hepatic resection. All SNPs were genotyped by sequencing DNA isolated from tumor samples of 483 patients with HBV-related HCC. We identified rs9275572 and HLA-DQB1 haplotype CCCCC (constituted by rs1130375C, rs12722107C, rs12722106C, rs36222416C and rs3189152C) were significantly associated with overall survival (OS) of HBV-related HCC patients (P=0.015 and 0.049, respectively), after adjusting for serum AFP level, the Barcelona Clinic Liver Cancer (BCLC) stages, Child-Pugh score, regional invasion, radical hepatic resection and adjuvant antiviral treatment. In stratified analyses, the AG/GG genotype of rs9275572 significantly decreased risk of death among patients with younger age, serum AFP levels ≥400ng/mL, tumor size ≥10cm, BCLC stage A and radical hepatic resection. HLA-DQB1 haplotype CCCCC was significantly protective for male patients, patients with serum AFP levels <400ng/mL, tumor size ≥10cm, BCLC stage B/C, postoperative adjuvant TACE/TAC/TAE, radical hepatic resection and patients with adjuvant antiviral treatment. Moreover, gene-dosage effects were also observed, patients with SNP rs9275572 AG/GG genotypes and Block2 CCCCC haplotype had a decreased risk of death compared to others after adjusting for serum AFP level, BCLC stages, Child-Pugh score, regional invasion, radical hepatic resection and adjuvant antiviral treatment (adjusted HR=0.38, 95% CI=0.20-0.73, P=0.004). The AG/GG genotype of rs9275572 and HLA-DQB1 Block2 CCCCC haplotype may have protective effects in HBV-related HCC patients receiving hepatic resection.
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