ASSOCIATION BETWEEN MICROSATELLITES WITHIN THE HUMAN MHC AND NASOPHARYNGEAL CARCINOMA

Nasopharyngeal carcinoma (NPC) has been known to be associated with sp ecific HLA haplotypes, in particular HLA A2, B46 and A33, B58 haplotyp es. A linkage study based on this observation suggested that HLA antig ens are not the cause of NPC but that there exists a gene that lies cl ose to if not within the major histocompatibility complex locus and co nfers a greatly increased relative risk of NPC. Since then, no further work has elucidated the presence of this gene. One of the difficultie s faced by researchers has been the size of the region of chromosome i mplicated. The MHC locus alone is almost 4 Mb in length, and the numbe r of genes encoded within it is numerous. The purpose of our study was thus to reduce the region of DNA in which the NPC susceptibility gene is likely to be. We report that the NPC susceptibility gene may be wi thin the centromeric end of the class-I and the telomeric end of the c lass-III regions of the MHC, near the D6S 1624 microsatellite locus, w here the presence of allele 4 of the microsatellite conferred a 3 1/2- fold increase in the risk of NPC, the highest reported for a single lo cus, and the presence of allele I of the same microsatellite conferred a highly significant protective effect against NPC. (C) 1997 Wiley-Li ss, Inc.