Original articlePolymorphisms of HLA-DQB1 predict survival of hepatitis B virus-related hepatocellular carcinoma patients receiving hepatic resection

SummaryObjectiveHuman 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.MethodologyAll SNPs were genotyped by sequencing DNA isolated from tumor samples of 483 patients with HBV-related HCC.ResultsWe identified rs9275572 and HLA-DQB1 haplotype CCCCC (constituted by rs1130375 C, rs12722107 C, rs12722106 C, rs36222416 C and rs3189152 C) 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 ≥ 400 ng/mL, tumor size ≥ 10 cm, BCLC stage A and radical hepatic resection. HLA-DQB1 haplotype CCCCC was significantly protective for male patients, patients with serum AFP levels <400 ng/mL, tumor size ≥ 10 cm, 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).ConclusionsThe AG/GG genotype of rs9275572 and HLA-DQB1 Block2 CCCCC haplotype may have protective effects in HBV-related HCC patients receiving hepatic resection.