title: KIR and HLA loci are associated with hepatocellular carcinoma development in patients with hepatitis B virus infection: a case-control study.
abstract: BACKGROUND
  Natural killer (NK) cells activation has been reported to contribute to inflammation and liver injury during hepatitis B virus (HBV) infection both in transgenic mice and in patients. However, the role of NK cells in the process of HBV-associated hepatocellular carcinoma (HCC) development has not been addressed. Killer cell immunoglobulin-like receptors (KIRs) are involved in regulating NK cell activation through recognition of specific human leukocyte antigen (HLA) class I allotypes.
  
  
  RESULTS
  To investigate whether KIR and HLA genes could influence the risk of HBV-associated HCC development, 144 HBV-infected patients with HCC and 189 well-matched HBV infectors with chronic hepatitis or cirrhosis as non-HCC controls were enrolled in this study. The presence of 12 loci of KIR was detected individually. HLA-A, -B, -C loci were genotyped with high-resolution. HLA-C group 1 homozygote (OR = 2.02; p = 0.005), HLA-Bw4-80I (OR = 2.67; p = 2.0E-04) and combination of full-length form and 22 bp-deleted form of KIR2DS4 (KIR2DS4/1D) (OR = 1.89; p = 0.017) were found associated with HCC incidence. When the combined effects of these three genetic factors were evaluated, more risk factors were observed correlating with higher odds ratios for HCC incidence (P trend = 7.4E-05). Because all the risk factors we found have been reported to result in high NK cell functional potential by previous studies, our observations suggest that NK cell activation may contribute to HBV-associated HCC development.
  
  
  CONCLUSIONS
  In conclusion, this study has identified significant associations that suggest an important role for NK cells in HCC incidence in HBV-infected patients. Our study is useful for HCC surveillance and has implications for novel personalized therapy strategy development aiming at HCC prevention in HBV-infected patients.
authors: Department of Immunology and pathogen biology, Southeast University Medical School, Nanjing, Jiangsu Province, China.
authors: Ning
authors: N
authors: Pan
authors: Wei
authors: W
authors: Jiang
authors: Hang
authors: H
authors: Sun
authors: Fengqin
authors: F
authors: Miao
authors: Jie
authors: J
authors: Qiu
authors: Hui
authors: H
authors: Jin
authors: Jinhuan
authors: J
authors: Xu
authors: Qian
authors: Q
authors: Shi
authors: Wei
authors: W
authors: Xie
authors: Jianqiong
authors: J
authors: Zhang
mesh_terms: D000328:Adult; D006528:Carcinoma, Hepatocellular / Q000150:complications / Q000235:genetics* / Q000821:virology; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D006509:Hepatitis B / Q000150:complications*; D006801:Humans; D007694:Killer Cells, Natural / Q000378:metabolism; D008113:Liver Neoplasms / Q000150:complications / Q000235:genetics* / Q000821:virology; D008297:Male; D008875:Middle Aged; D054340:Receptors, KIR / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D054340:Receptors, KIR