Association Of Killer Cell Immunoglobulin-like Receptor Gene Polymorphisms With Nasopharyngeal Carcinoma

BACKGROUND Nasopharyngeal carcinoma (NPC), one of malignant tumor in southern China, has a remarkably distinctive ethnic and geographic distribution. The highest incidence is found among southern Chinese (25～30 per 100, 000 persons per year), especially those of Cantonese origin. In the year of 2000, 64 798 new cases were registered all over the world, more than 80% of which were reported from China, Southeast Asia, and some other Asian countries. In contrast, NPCis a rare malignant disease, with an incidence well under 1 per 100 000 persons per year in Caucasians from North America and other western countries.There are three major etiological factors, including genetic, environmental, and viral factors in development of NPC. Southern Chinese immigrants also have a higher risk of NPCcompared with local western population. This suggests a strong association of NPCwith genetic factors.KIRgenes are highly polymorphic. In addition, KIRgene can be a genetic mark to study hereditary disease and virus induced cancer, such as cervical and liver cancers.Previous studies have convincingly shown the association of HLAalleles involved in adaptive immunity with NPC. However, no studies to date have examined NPCrisk in the context of innate immunity. Natural killer (NK) cells, which are modulated through activating and inhibitory receptors, are necessary elements of innate immunity. Among the NKcell (and other effector cell) receptors, the killer cell immunoglobulin-like receptors (KIR) are by far the most polymorphic ones. This family of receptors consists of both activating and inhibitory allotypes. Inhibitory KIRs interact with specific MHCⅠmolecules to impede NKcytolysis and protect "self" cells from spontaneous destruction, whereas activating receptors, presumably the activating KIR, stimulate directed destruction of NKcell to target cells including transformed tumor cells, virus infected cells, and cells undergoing other types of "stress".OBJECTIVE To investigate the association between the killer cell immunoglobulin-like receptor ( KIR) gene polymorphisms and nasopharyngeal carcinoma(NPC). Also to study whether the polymorphisms of KIRis different between the NPCpatients and the controls. To determine whether there is a difference between different areas with higher or lower incidence, we also compare KIRgenes of NPCpatients of Cantonese origin with those of other origins. METHODS All 43 NPCpatients and 53 randomly ethnically matched healthy controls were enrolled to detect the KIRgenotype using PCR/SSP in Guangdong Han population. At the same time, we study the genotype of those 43 Cantonese NPCcontainning 32 patients from other Provinces of China.RESULTS 18 KIRgenes were identified. The frequencies of KIR3DL3, 3DL2 and 2DL4 are 100%. The 2DL2, 2DS1, 2DS3, 2DS4 gene frequencies were significantly higher in the patient group(P=0.035, 0.002, 0.007, 0.001)than in the control group. The rest was found to have no significant difference compared with the healthy controls. Genotype of those Cantonese NPCwere found to have no significant difference compared with those from other provinces. By historical comparison, it was seem that the frequencies of 3DS1, 2DS4 gene were significantly higher than that of the patient group. The Cantonese own their characteristics in the Polymorphism of KIR.CONCLUSIONS1. There may be association between pathogenesis of NPCand 3DS1, 2DS4 genes in Chinese.2. It couldn't prove that there was significant correlation in KIRgene frequencies between the Cantonese NPC with those from other provinces.3. There may be association between pathogenesis of NPC and 2DL2, 2DS1, 2DS3, 2DS4 genes in Cantonese origin.4. Different KIR genes have different expression frequencies in Guangdong Han population, and KIRgene distribution changes in populations of other 4 areas.