Combination of Human Leukocyte Antigen and Killer Cell Immunoglobulin-Like Receptor Genetic Background Influences the Onset Age of Hepatocellular Carcinoma in Male Patients with Hepatitis B Virus Infection

Abstract

To investigate whether killer cell immunoglobulin-like receptor(KIR)and human leukocyte antigen(HLA)genetic background could influence the onset age of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) infection, one hundred and seventy-one males with HBV-related HCC were enrolled. The presence of 12 loci ofKIRwas detected individually.HLA-A, -B, and -Cloci were genotyped with high resolution by a routine sequence-based typing method. The effect of eachKIRlocus,HLAligand, andHLA-KIRcombination was examined individually by Kaplan-Meier (KM) analysis. Multivariate Cox hazard regression model was also applied. We identifiedC1C1-KIR2DS2/2DL2as an independent risk factor for earlier onset age of HCC (median onset age was 44 forC1C1-KIR2DS2/2DL2positive patients compared to 50 for negative patients,P=0.04for KM analysis; HR = 1.70,P=0.004for multivariate Cox model). We conclude thatKIRandHLAgenetic background can influence the onset age of HCC in male patients with HBV infection. This study may be useful to improve the current HCC surveillance program in HBV-infected patients. Our findings also suggest an important role of natural killer cells (or otherKIR-expressing cells) in the progress of HBV-related HCC development.