Hodgkin's disease susceptibility: linkage to the HLA locus demonstrated by a new concordance method.

The role of genetic susceptibility in the pathogenesis of Hodgkin's Disease has been considered relatively minor because of the rarity of familial disease, the absence of an identified pattern of inheritance, and the weakness of HLA associations in population studies. The availability of four prospectively ascertained HD families permitted reappraisal of the cosegregation of HLA and HD susceptibility by a new extended concordance analysis method. HLA haplotype concordance among patients was greater than that expected by chance alone for our four families (P less than 0.022) and also for these in combination with twelve informative families in the literature (P less than 0.0015). This study thus provides a new method, based on genotype concordance of affected relatives, for assessing linkage of HLA and disease susceptibility, and new evidence for the genetic control of susceptibility to HD. The model presented, as well as alternative and more complex models, points to the existence of an HD susceptibility gene in or near the HLA region, which, in the presence of a suitable etiologic agent or additional genetic susceptibility, leads to the induction of HD.