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Clinical and Developmental Immunology
Volume 2013, Article ID 874514, 7 pages
Research Article

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

1Department of Pathogenic Biology and Immunology, Southeast University Medical School, 87 Dingjiaqiao Road, Nanjing, Jiangsu 210009, China
2Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, Southeast University, Nanjing, Jiangsu 210009, China
3The Second Affiliated Hospital of Southeast University, Nanjing, Jiangsu 210000, China
4Department of Epidemiology, School of Public Health, Southeast University, Nanjing, Jiangsu 210009, China

Received 15 July 2013; Revised 17 September 2013; Accepted 17 September 2013

Academic Editor: Saied Mirshahidi

Copyright © 2013 Ning Pan et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.