FaCD Online Syndrome Fact Sheet

Last updated: 01 Jul 2008

Name: Hodgkin disease, Familial Clustering of

Synonym: Hodgkin Lymphoma, Familial Clustering of

Mode of Inheritance: AR?/ multifact?

Tumor features

Hodgkin disease (Hodgkin's lymphoma)

Comment

Familial clustering of Hodgkin disease (HD) has been reported for many years[1;2]. This clustering is most often observed in siblings[3;4] and may reflect an age-specific genetic susceptibility to HD[5], possibly because of susceptibility to an environmental agent[6]. Haim et al.[7] found four pairs of affected first-degree relatives among a series of 183 patients (relative risk (RR= 9). Anticipation has been observed in HD and NHL families[19]. In general, the relative risk to develop HD in a first-degree relative of an affected patient is estimated at approximately 3[8,17].

Grufferman et al.[9] found that siblings of the same sex as an affected person had a risk of HD double that of siblings of the opposed sex. The authors suggested that siblings of the same sex might share more (intensely) environmental risk factors. In a Scottish population, a 4-fold increase in deaths due to HD was found among first and second degree relatives of patients with HD[15]. Mack et al.[10] observed that monozygotic twins of patients with HD were at an increased risk (RR 99) to develop HD, whereas dizygotic twins were not. Ferraris et al.[11] reviewed cases of familial HD published between 1972 and 1995 and concluded that the male-to-female ratio in familial HD is 1.5, similar to the ratio in sporadic HD; only one major incidence peak was observed (15-34 years) as opposed to the 2 peaks seen in sporadic HD[2]. Shugart et al.[12] observed that when children of a parent with HD also developed this disorder, they did so at an age which was on average 13 years younger than the time of diagnosis in their parents (referred to as "anticipation" ). The authors estimated the heritability of HD in the Swedish population to be 28.4%.

In a study on Swedish and Danish populations the risk of HD in relatives of patients with HD was shown to be increased, with relative risks of 3.5 [95% CI], 1.8-6.8) in Sweden and 2.6 (95% CI, 1.0-6.5) in Denmark and a pooled estimate of 3.11 (95%CI, 1.8-5.3). Relative risks were higher in males and in siblings and in relatives of patients with earlier-onset disease (<40 yrs)[17]. HD has been observed in association with familial cases of other types of hematolymphoproliferative disorders (see: hemato-lymphoproliferative disease, familial clustering)[20]. In the Swedish population, there is an approximately twofold increased risk of NHL and HD among individuals with a family history of hematopoietic malignancy[18]. Germline p53 mutations, associated with Li-Fraumeni syndrome, are not a common cause of familial lymphomas[13,14]. A familial association of multiple sclerosis and young-adult-onset Hodgkin lymphoma has been observed[16].

References

[1] Razis DV, Diamond HD, Craver LF. Familial Hodgkin's disease: its significance and implications. Ann Intern Med 1959; 51:933-971.
[2] Grufferman S. Hodgkin's disease. In: Schottenfeld D, editor. Cancer epidemiology and prevention. Philadelphia: Saunders, 1982: 739-753.
[3] Paltiel O, Schmit T, Adler B, Rachmilevitz EA, Polliack A, Cohen A, Haim N, Shachar MB, Epelbaum R, Barchana M, Cohen R, Yehuda DB. The incidence of lymphoma in first-degree relatives of patients with Hodgkin disease and non-Hodgkin lymphoma: results and limitations of a registry-linked study. Cancer 2000; 88(10):2357-2366.
[4] Shugart YY, Collins A. Combined segregation and linkage analysis of 59 Hodgkin's disease families indicates the role of HLA determinants. Eur J Hum Genet 2000; 8:460-463.
[5] Siebert R, Louie D, Lacher M, Schluger A, Offit K. Familial Hodgkin's and non-Hodgkin's lymphoma: Different patterns in first-degree relatives. Leuk Lymphoma 27[5-6], 503-507. 1997.
[6] Vianna NJ, Polan AK, Davies JNP, Wolfgang P. Familial Hodgkin's disease: an environmental and genetic disorder. Lancet 1974; II:854-857.
[7] Haim N, Cohen Y, Robinson E. Malignant lymphoma in first-degree blood relatives. Cancer 1982; 49(10):2197-2200.
[8] Fraumeni jr JF. Family studies in Hodgkin's disease. Cancer Res 1974; 34:1164-1165.
[9] Grufferman S, Cole P, Smith PG, Lukes RJ. Hodgkin's disease in siblings. N Engl J Med 1977; 296(3):248-250.
[10] Mack TM, Cozen W, Shibata DK, Weiss LM, Nathwani BN, Hernandez AM, Taylor CR, Hamilton AS, Deapen DM, Rappaport EB. Concordance for Hodgkin's disease in identical twins suggesting genetic susceptibility to the young-adult form of the disease. N Engl J Med 1995; 7:413-418.
[11] Ferraris AM, Racchi O, Rapezzi D, Gaetani GF, Boffetta P. Familial Hodgkin's disease: a disease of young adulthood? Ann Hematol 1997; 74:131-134.
[12] Shugart YY, Hemminki K, Vaittinen P, Kingman A, Dong C. A genetic study of Hodgkin's lymphoma: an estimate of heritability and anticipation based on the familial cancer database in Sweden. Hum Genet 2000; 106(5):553-556.
[13] Weintraub M, Lin AY, Franklin J, Tucker MA, Magrath IT, Bhatia KG. Absence of germline p53 mutations in familial lymphoma. Oncogene 1996; 12(3):687-91.
[14] Pötzsch C, Schaefer HE, Lübbert M. Familial and metachronous malignant lymphoma: absence of constitutional p53 mutations. American journal of hematology 1999; 62(3):144-9.
[15] Kerzin-Storrar L, Faed MJ, MacGillivray JB, Smith PG. Incidence of familial Hodgkin's disease. British journal of cancer 1983; 47(5):707-12.
[16] Hjalgrim H, Rasmussen S, Rostgaard K, Nielsen NM, Koch-Henriksen N, Munksgaard L, Storm HH, Melbye M. Familial clustering of Hodgkin lymphoma and multiple sclerosis. Journal of the National Cancer Institute 2004; 96(10):780-4.
[17] Goldin LR, Pfeiffer RM, Gridley G, Gail MH, Li X, Mellemkjaer L, Olsen JH, Hemminki K, Linet MS. Familial aggregation of Hodgkin lymphoma and related tumors. Cancer 2004; 100(9):1902-8.
[18] Chang ET, Smedby KE, Hjalgrim H, Porwit-MacDonald A, Roos G, Glimelius B, Adami HO. Family history of hematopoietic malignancy and risk of lymphoma. Journal of the National Cancer Institute 2005; 97(19):1466-74.
[19] Alexandrescu DT, Garino A, Brown-Balem KA, Wiernik PH. Anticipation in families with Hodgkin's and non-Hodgkin's lymphoma in their pedigree. Leukemia & lymphoma 2006; 47(10):2115-27.
[20] Rudant J, Menegaux F, Leverger G, Baruchel A, Nelken B, Bertrand Y, Hartmann O, Pacquement H, Vérité C, Robert A, Michel G, Margueritte G, Gandemer V, Hémon D, Clavel J. Family history of cancer in children with acute leukemia, Hodgkin's lymphoma or non-Hodgkin's lymphoma: the ESCALE study (SFCE). International journal of cancer 2007; 121(1):119-26.