This has an incidence of 2–3 per 100,000 population in the UK. Analysis of the age at onset of Hodgkin disease reveals a bimodal distribution, with one peak around the age of 25 years, then decreasing to a plateau in middle age, after which rates increase with advancing age for the second peak. The disease is more common in males than in females, in people of higher socioeconomic status, and in smaller families. The etiology of Hodgkin disease is unknown, but an infective agent has been suggested, particularly in the younger age group and in the nodular sclerosis subtype. An association between familial clustering of multiple sclerosis and young-adult-onset Hodgkin lymphoma (HL) has been reported and suggests that the two conditions share environmental and/or constitutional factors (Hjalgrim et al. 2004; Shugart et al. 2000).
Ferraris et al. (1997) reviewed the literature on familial Hodgkin disease. They confirmed an excess of males in familial cases, that the male-to-female ratio (1.5:1) was similar in familial and sporadic cases, and that the age distribution of familial cases shows a single major peak between 15 and 34 years of age. Both genetic and environmental (e.g., viral infections) factors have been implicated in familial clustering of Hodgkin disease. Analysis of 432 sets of twins affected by Hodgkin disease revealed that 0 of 187 dizygotic twins were concordant for Hodgkin disease, compared to 10 of 179 monozygotic twins – expected cases >0.1 for each group (Mack et al. 1995). The higher concordance in monozygotic twins compared to dizygotic twins clearly implicates genetic factors in familial clustering of Hodgkin disease in young adults. In a study of Hodgkin disease in Sweden, Shugart et al. (2000) estimated the heritability to be 28 % and suggested that there was significant evidence for anticipation in parent–child pairs with Hodgkin disease (mean difference 14 years). The relative risk of HL in relatives of cases is about 3.1, and there is also an increased relative risk for chronic lymphatic leukemia and non-Hodgkin lymphoma, and these relative risks are higher in relatives of young-onset cases (Goldin et al. 2004).
Epidemiological evidence suggests that Hodgkin disease may be a rare outcome of a specific infective agent, possibly Epstein–Barr virus (EBV). However EBV infection is common and often asymptomatic suggesting that additional factors, such as inherited immune response variants, might be implicated in susceptibility to Hodgkin disease. Hence a number of groups have investigated the associations between Hodgkin disease and HLA loci. Linkage studies in multiple-case families have confirmed an association with a susceptibility gene at the HLA locus and are consistent with a recessive gene which would account for a twofold increase in relative risk for siblings of patients with Hodgkin disease (Chakravarti et al. 1986). Linkage to the HLA class II region has also been demonstrated (Klitz et al. 1994); in particular, alleles at the HLA-DPB1 locus have been implicated specific histological subtypes, and an association with EBV-positive cases has been suggested (Taylor et al. 1999; Alexander et al. 2001). A recent assessment suggests that HL A determinants contribute additively with one or more other genes to susceptibility to Hodgkin’s (Shugart and Collins 2000). There is an increased incidence of Hodgkin disease in immunodeficient patients, and it accounts for about 10 % of Tumours associated with primary immunodeficiency disorders. The mean age at diagnosis of Hodgkin disease in immunodeficient patients is 10.9 years, although there was a wide range, from less than 1–73 years (Kersey et al. 1988). Compared to pediatric
patients with Hodgkin disease and no immunodeficiency disorder, there is an excess of mixed cellularity and lymphocyte depletion subtypes. However, most lymphomas that occur in immunodeficient individuals are categorized as non-Hodgkin lymphoma. The recent finding of chromosomal rearrangements involving JAK2, t(4;9)(q21;p24) JAK2 rearrangements, including the novel SEC31A-JAK2 fusion, which are recurrent in classical Hodgkin lymphoma, is of importance; the t(4;9)(q21;p24) leads to a novel SEC31A-JAK2 fusion which is oncogenic in vitro and acts as a constitutively activated tyrosine kinase that is sensitive to JAK inhibitors (Van Roosbroeck et al. 2011).
Germline mutations in NPAT (nuclear protein ataxia-telangiectasia locus) have been found to segregate with nodular lymphocyte predominant Hodgkin’s lymphoma in a family and have also been detected in sporadic cases of the disease, suggesting that these mutations confer an increased risk (OR = 4.11) of this condition (Saarinen et al. 2011a, b).