The role of human leucocyte antigen genes in the development of malignant disease

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Introduction The human leucocyte antigen (HLA) class I and in particular class II genes play a major role in regulating the immune response. The extensive polymorphism of these genes has been characterised by a series of international histocompatibility workshops undertaken during the past 31 years, with the current (Twelfth) workshop due to conclude in St Malo in June 1996. Many studies, both within and without these workshops, have revealed significant associations between particular polymorphisms of the HLA class I and especially class II genes and predisposition to a large number ofbenign, immune system mediated diseases including rheumatoid arthritis,' coeliac disease,2 insulin dependent diabetes,3 multiple sclerosis,4 Graves's disease,5 and IgE responsiveness to various pollen and animal dander allergens.6 HLA class II allelic associations have also been detected in other benign conditions with no obvious immunological component, such as narcolepsy.7 However, the first HLA and disease association to be reported in 1967 was between the HLA class I B35, B5 and B18 group of alleles (then known as 4C) and a malignant condition-Hodgkin's disease.8 Nevertheless, until recent years there has been comparatively little interest in HLA genetic polymorphism and predisposition to malignant diseases. This has now changed, particularly since the advent of accurate, high resolution DNA based methods for analysis ofHLA polymorphism. A small but growing literature now exists relating HLA class II polymorphism and predisposition to a number of malignancies. In addition, downregulation of HLA class I expression on tumour cells would seem to be a frequent route by which tumour cells escape from T cell mediated attack. These more recent findings will be outlined below.