Abstract
Both targeted and genome-wide studies have revealed genetic associations for susceptibility, prognosis, and treatment-induced secondary malignancies and toxicities in classical Hodgkin lymphoma (cHL). This review gives a systematic and comprehensive overview of significant associations and places them into a biologic context. The strongest susceptibility polymorphisms have been found for the human leukocyte antigen (HLA) genes. These associations are specific for cHL overall or for subgroups based on tumor cell Epstein-Barr virus (EBV) status. These findings strongly suggest that EBV-specific immune responses influence cHL susceptibility in EBV(+) cHL and that immune responses targeting other tumor-associated antigens are important in EBV(-) cHL. Accordingly, most of the numerous other susceptibility loci map to genes that affect functionality of the immune system, underscoring the crucial role of the immune system in cHL development. The number of association studies on cHL prognosis is limited with one consistent association for the drug-metabolizing UGT1A1 gene. PRDM1 is associated with radiation-induced secondary malignancies and a small number of genes are associated with treatment-related toxicities. In conclusion, most loci showing genetic associations in cHL harbor genes with a potential functional relevance for cHL susceptibility.
Highlights
Classical Hodgkin lymphoma is a B-cell malignancy that is characterized by a minority of large, sporadically binucleated tumor cells, called Hodgkin Reed– Sternberg (HRS) cells
Epstein–Barr virus (EBV) is observed at higher frequencies in children and elderly Classical Hodgkin lymphoma (cHL) patients with the mixed cellularity (MC) subtype, whereas young adult patients with cHL usually are diagnosed with EBVÀ nodular sclerosis (NS) subtype [5]
If the same SNP was analyzed in multiple studies, we looked for consistency of the results
Summary
Classical Hodgkin lymphoma (cHL) is a B-cell malignancy that is characterized by a minority of large, sporadically binucleated tumor cells, called Hodgkin Reed– Sternberg (HRS) cells. On the basis of the background architecture and the composition of the microenvironment, cHL can be subdivided into four histologically defined subgroups, with nodular sclerosis (NS) being the most common subtype representing approximately 70% to 80% of all cases. Note: Supplementary data for this article are available at Cancer Epidemiology, Biomarkers & Prevention Online (http://cebp.aacrjournals.org/). Long-term survivors frequently suffer from treatment-related adverse effects, such as cardiac disease and secondary malignancies [13]. Numerous studies have been carried out to find genetic cHL susceptibility associations, as well as associations with cHL prognosis and risk of treatment-related late adverse effects. We critically review these studies and comment on the possible biologic relevance of reported findings
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