title: Human leukocyte antigens and genetic susceptibility to lymphoma.
abstract: Familial aggregation, coupled with ethnic variation in incidence, suggests that inherited susceptibility plays a role in the development of lymphoma, and the search for genetic risk factors has highlighted the contribution of the human leukocyte antigen (HLA) complex. In a landmark study published almost 50 years ago, Hodgkin lymphoma (HL) was the first disease to be associated with HLA variation. It is now clear that Epstein-Barr virus (EBV)-positive and -negative HL are strongly associated with specific HLA polymorphisms but these differ by EBV status of the tumours. HLA class I alleles are consistently associated with EBV-positive HL while a polymorphism in HLA class II is the strongest predictor of risk of EBV-negative HL. Recent investigations, particularly genome-wide association studies (GWAS), have also revealed associations between HLA and common types of non-Hodgkin lymphoma (NHL). Follicular lymphoma is strongly associated with two distinct haplotypes in HLA class II whereas diffuse large B-cell lymphoma is most strongly associated with HLA-B*08. Although chronic lymphocytic leukaemia is associated with variation in HLA class II, the strongest signals in GWAS are from non-HLA polymorphisms, suggesting that inherited susceptibility is explained by co-inheritance of multiple low risk variants. Associations between B-cell derived lymphoma and HLA variation suggest that antigen presentation, or lack of, plays an important role in disease pathogenesis but the precise mechanisms have yet to be elucidated.
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: K A
authors.initials: KA
authors.lastname: McAulay
authors.affiliation: MRC - University of Glasgow Centre for Virus Research, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
authors.forename: R F
authors.initials: RF
authors.lastname: Jarrett
mesh_terms: D000483:Alleles; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D015870:Gene Expression; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes; D004854:Herpesvirus 4, Human / Q000472:pathogenicity / Q000502:physiology; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000235:genetics* / Q000276:immunology; D006689:Hodgkin Disease / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000150:complications / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D020641:Polymorphism, Single Nucleotide
chemical_list: D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II
keywords: B-cell lymphoma; Epstein-Barr virus; Hodgkin lymphoma; human leukocyte antigen