Genetic susceptibility to Hodgkin's lymphoma and to secondary cancer: workshop report

Although the occurrence of familial Hodgkin's lymphoma (HL) is a rare event, genetic susceptibility as a cause of HL and its influence on treatment outcome may not be rare. However, results obtained from the analysis of HL families will probably have broad implications with regard to understanding common pathogenic factors leading to the development of the disease. The description of anticipation among the affected offspring of HL patients further strengthens the view that heritable factors contribute to development of HL. Moreover, the finding that particular human leukocyte antigen (HLA) alleles are associated with susceptibility to HL may be regarded as a hint to the presence of an as yet undefined infectious agent, leading to the growth of a malignant lymphoma cell clone in those patients that are more susceptible to this agent due to their HLA genotype. In addition, since an intrinsic genomic instability was observed in a proportion of HL patients, it is plausible that these patients are not only susceptible to the causation of HL, but are also at a higher risk of developing therapy-related (TR) secondary cancers following treatment. Estimation of sister chromatid exchange was established as a tool to identify patients at higher risk of TR cancer. In this context the use of therapeutic agents known to increase genomic instability should be carefully considered prior to determing the best treatment. The future identification of heritable factors contributing to HL will be of importance both with regard to diagnosis as well as treatment of HL patients.