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Nasopharyngeal carcinoma (NPC) is a highly prevalent Epstein-Barr virus (EBV) associated disease in Southern China, where host genetic factors play a critical role in the disease pathogenesis. Thus far, systematic study on human leukocyte antigen (HLA) polymorphism in Hong Kong Chinese with NPC has been lacking. To identify the association between different HLA alleles and NPC in Hong Kong Chinese, we performed this first case-control study. Using high-resolution typing of HLA class I (A, B and Cw) and II (DRB1, DRB3-5 and DQB1) genes by sequence-specific oligonucleotide probes (SSOP) and sequence-based typing (SBT), we determined and compared the HLA alleleic frequencies of 100 NPC patients with 100 age- and sex-matched healthy blood donors after informed consent. The 5 most frequent HLA-A types in the NPC group observed were A*0207 (38.57%), A*110101 (28.57%), A*330301 (22.86%), A*2402 (20%) and A*020301 (15.71%). In this study, we confirmed again previous observations of positive (susceptible) association of A*0207 and B*460101 with NPC. More importantly, we first identified the negative (resistant) association of A*020601 (p=0.0192, odds ratio (OR)=0.28) and positive association of Cw*01 (p=0.0001, OR=3.19) with NPC. Negative association of A*110101, B*40, Cw*12, Cw*14 and Cw*15 with NPC were also identified. Positive association of certain allelic combinations particularly A*0207-Cw*01-B*460101 (p<0.0001, OR=4.10) and A*0207-Cw*01-B*460101-DRB1*09-DQB1*03 (p<0.0001, OR=42.13) were first observed. The importance of these novel findings will be further validated by Phase II study. In conclusion, the strong association of certain HLA alleles and allelic combinations with NPC again confirms the important role of immunogenetics in NPC pathogenesis and the strong Ethnic association of the disease.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA