NPC is an epithelial tumor that is highly prevalent among the southern Chinese. Numerous studies have indicated that specific HLA haplotypes and genes within the HLA complex are associated with NPC. As a first effort to localize the gene responsible for susceptibility, the HLA-A, -B, and -A2 subtypes were examined for their association to NPC. Consistent with previous reports, frequencies of HLA-A2 [OR ‫؍‬ 2.50, pc ‫؍‬ 0.020 (study population); OR ‫؍‬ 3.73, pc ‫؍‬ 0.0030 (>40 years old)] were significantly higher in patients with NPC than in healthy controls. Two-locus analysis indicated that A2 ؉ B46؉ individuals are at greater risk for NPC than A2 -B46 -individuals in both the population studied and the >40-year-old group. This, however, may be due to the close linkage of these 2 genes. Moreover, A2 ؉ B38؉ individuals were at higher risk than A2 -B38 -individuals in both the population studied and the >40-year-old group; A2 and B38 are not genetically linked. These findings suggest that B38 or B46 alone cannot confer a high risk of NPC but that, in conjunction with A2, B38 or B46 positivity greatly increases risk. None of 5 A2 subtypes identified from studied populations was significantly associated with NPC. Microsatellite marker D6S211, located 97 kb telomeric to HLA-A, was analyzed for its association with NPC. Allele 4 of D6S211 was significantly associated with NPC (OR ‫؍‬ 3.97, pc ‫؍‬ 0.0042). These results strongly support the hypothesis that genes associated with susceptibility to NPC in the HLA region are within the HLA-A locus.

Nasopharyngeal carcinoma (NPC) is an epithelial tumor uniquely prevalent in southern Chinese. HLA-A2 is associated with NPC. In a previous study, we showed that the genes associated with susceptibility to NPC are primarily located within the HLA-A locus in Taiwanese NPC patients. However, the pathogenic genes causing NPC susceptibility remain unknown. Here, 8 polymorphic microsatellite markers distributed over a 1 megabase region surrounding the HLA-A locus were subjected to genetic analysis for the NPC-susceptibility locus. Statistical studies of associated alleles detected on each microsatellite locus showed that the NPCsusceptibility genes are most likely located between the D6S510 and D6S211 markers within a 132 kb segment containing the HLA-A locus. These results undoubtedly would facilitate the further positional cloning of the NPC-susceptibility locus, which has been elusive for the past 30 years. ' 2005 Wiley-Liss, Inc.