Familial aggregation of Hodgkin lymphoma and related tumors

Abstract

BACKGROUND The importance of genetic factors in the etiology of Hodgkin lymphoma (HL) has been suggested by family and population studies. However, the spectrum of malignancies associated with common genetic etiology and the effects of gender and age on familial risk have not been established. METHODS Diagnoses of lymphoproliferative malignancies were compared in 15,799 first‐degree relatives of 5047 patients with HL versus 32,117 first‐degree relatives of 10,078 control probands from Sweden and in 7185 first‐degree relatives of 2429 patients with HL versus 27,434 first‐degree relatives of 8,495 control probands from Denmark using marginal survival models. RESULTS The risk of HL in relatives of patients with HL was increased significantly in both populations, with relative risks of 3.47 (95% confidence interval [95% CI], 1.77–6.80) in Sweden and 2.55 (95% CI, 1.01–6.45) in Denmark and a pooled estimate of 3.11 (95%CI, 1.82–5.29). In Sweden, risks for relatives of patients also were increased significantly for chronic lymphocytic leukemia and non‐Hodgkin lymphoma (in males). Relative risks were higher in males compared with females and in siblings of patients compared with parents and offspring of patients. Relatives of patients with earlier‐onset disease were at higher risk for HL. CONCLUSIONS HL has an important familial component, which is stronger in families of affected individuals age < 40 years, in males, and in siblings, and it is shared with some (but not other) lymphoproliferative malignancies. The cumulative lifetime risks are very small, however, for the development of HL de novo or in first‐degree relatives of affected patients. Cancer 2004. Published 2004 by the American Cancer Society.

The familial risk of Hodgkin's lymphoma ranks among the highest in the Swedish Family-Cancer Database

“…We confirmed and further quantified the strong familial clustering of HL, [1][2][3][4][5][6] being among the highest for any malignancy in the Database; the sibling risk of over 5 ranks second after testicular cancer. 9 The higher risks for siblings compared to parent-offspring pairs suggest a recessive component or childhood shared effects.…”

“…Despite evidence suggesting a familial clustering of Hodgkin's lymphoma (HL), [1][2][3][4][5][6] there is no clear understanding on the relative contribution of genes and shared environmental factors, including childhood infections, 7,8 to familial risk. The rarity of familial HL has hampered a detailed analysis of the familial clustering and it has probably contributed to the variation even in recent risk estimates for first-degree relatives, such as 4.9 from Utah 5 and 3.27 from Iceland.…”

Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene

“…2 Specifically, there is strong evidence for genetic factors based on evidence from multiply affected families from case series, twin, case-control, and population-based registry studies. [3][4][5][6][7][8][9] Furthermore, our group analyzed data from registries in Scandinavia and found significant familial aggregation of HL (RR = 3.1) and other lymphoproliferative tumors. Relative risks were higher in men compared with women, in siblings of cases compared with parents and offspring, and in relatives of patients with diagnosis under the age of 40.…”

“…Relative risks were higher in men compared with women, in siblings of cases compared with parents and offspring, and in relatives of patients with diagnosis under the age of 40. 4 In addition, we showed that nonHodgkin lymphoma (NHL) also aggregates in HL families. The human leukocyte antigen (HLA) region on chromosome 6 has been associated with HL in several studies.…”

“…Whole exome sequencing in families at high risk for Hodgkin lymphoma: identification of a predisposing mutation in the KDR gene Melissa Rotunno, 1 Mary L. McMaster, 1 Joseph Boland, 2 Sara Bass, 2 Xijun Zhang, 2 Laurie Burdett, 2 Belynda Hicks, 2 Sarangan Ravichandran, 3 Brian T. Luke, 3 Meredith Yeager, 2 Laura Fontaine, 4 Paula L. Hyland, 1 Alisa M. Goldstein, 1 NCI DCEG Cancer Sequencing Working Group, NCI DCEG Cancer Genomics Research Laboratory, Stephen J. Chanock, 5 Neil E. Caporaso, 1 Margaret A. Tucker, 6 and Lynn R. Goldin 1 status and in smaller families; 4) the occurrence of EpsteinBarr virus (EBV) in HL tumor cells and 5) a strong familial risk. 2 Specifically, there is strong evidence for genetic factors based on evidence from multiply affected families from case series, twin, case-control, and population-based registry studies.…”