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
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 of KIR was detected individually. HLA-A, -B, and -C loci were genotyped with high resolution by a routine sequence-based typing method. The effect of each KIR locus, HLA ligand, and HLA-KIR combination was examined individually by Kaplan-Meier (KM) analysis. Multivariate Cox hazard regression model was also applied. We identified C1C1-KIR2DS2/2DL2 as an independent risk factor for earlier onset age of HCC (median onset age was 44 for C1C1-KIR2DS2/2DL2 positive patients compared to 50 for negative patients, for KM analysis; HR = 1.70, for multivariate Cox model). We conclude that KIR and HLA genetic 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 other KIR-expressing cells) in the progress of HBV-related HCC development. 1. Introduction Primary liver cancer, particularly hepatocellular carcinoma (HCC), is the fifth most common cancer worldwide and the third most common cause of cancer mortality. The curative therapy for HCC is surgical resection, for which only the patients with early stage tumor are eligible. However, most cases of HCC patients are detected in their late stages and become ineligible for surgical resection. Globally, more than 50% of HCC are due to persistent hepatitis B virus (HBV) infection. In the hyperendemic areas of HCC, such as China and Africa, chronic HBV infection contributes to at least 80% of HCC cases [1]. Periodic screening for HCC in HBV-infected patients has been practiced widely and been found to be useful in detecting HCC at early stage [2, 3]. However, the current HCC screening is reported as borderline cost effective in the Asia-Pacific region, and the optimal screening program remains to be established [4, 5]. One of the controversial issues is that when to begin this periodic screening in HBV infectors due to a wide variety of onset age of HCC. Knowledge on the factors that influence the onset age of HCC will improve current HCC surveillance program in HBV-infected patients. Accumulating evidence from the last decade suggests that natural killer (NK) cells play an important role not only
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