FaCD Online Syndrome Fact Sheet

Last updated: 29 Dec 2008

Name: Hemato-Lymphoproliferative Disease, Familial Clustering of

Mode of Inheritance: AD?/ multifact?

Tumor features

Hodgkin disease (Hodgkin's lymphoma)
leukemia, acute lymphoblastic (ALL)
leukemia, acute myeloid (AML, incl. ANLL)
leukemia, chronic lymphocytic (CLL)
leukemia, chronic myeloid (CML)
multiple myeloma (Kahler's disease)
myelodysplastic syndrome (MDS)
non-Hodgkin lymphoma

Tumor features (possible)

breast cancer
cervical cancer
gastric cancer
hepatocellular cancer (hepatoma)
lung/bronchial cancer
ovarian cancer (i.e. epithelial origin)
pancreatic adenocarcinoma

Non-tumor features (possible)

excessive production of monoclonal IgM

Comment

Different types of hemato-lymphoproliferative disorders have been observed to cluster within the same families. Zhu et al.[1] observed that relative risk (RR) of non-Hodgkin lymphoma (NHL) was associated with a family history of lymphoma (RR 3.0) and hematological malignancies (RR 2.3). Risk of Hodgkin's disease was shown to be to be increased among relatives of early-onset (<50 years) NHL cases (HR, 3.2)[6].
Relatives of patients with CLL have an increased risk for chronic lymphocytic leukemia (CLL) ((RR] = 7.5), for NHL (RR = 1.5), and for Hodgkin lymphoma (RR = 2.4)[2].
Relatives of NHL cases are at increased relative risk for NHL (RR 1.7), Hodgkin lymphoma (RR 1.4). No increased risk was found for multiple myeloma among case relatives[3].
In a series of American women, those with a family history of lymphoma (OR 2.2) or leukemia (OR 2.5) had an increased risk of NHL. The risk was higher among women who had a sibling with lymphoma or leukemia than those who had parents with lymphoma or leukemia. The study also noted non-hematopoietic malignancies in first-degree relatives:cancer of the lung (OR 1.7) in first-degree relatives, stomach (OR 2.2) and pancreas (OR 2.6) in parents, as well as liver (OR = 5.0, 95%CI: 1.0-24.6), breast (OR = 2.2, 95%CI: 1.3-3.9), cervix (OR = 7.5, 95%CI: 0.9-64.9), and ovary (OR = 3.5, 95%CI: 1.1-11.5) in siblings were also associated with an increased risk of NHL.[7]

In a series of close to 2000 American patients with NHL or Hodgkin lymphoma (HL) or CLL, the following percentages of probands reported a first-degree relative with a related lymphoproliferative disorder: 13·3% of CLL probands, 8·8% of NHL probands and 5·9% of HL probands (P = 0·002). The prevalence of CLL was significantly increased in parents of CLL probands (P < 0·05). Fathers of NHL probands were more often reported to have had NHL than the mothers of those probands (P = 0·026).[10] A study from the Swedish Family Cancer Database stratified risks for NHL subtypes: a family history of NHL increased the risk for NHL (SIRparent = 1.8; SIRsibling = 1.9) and for diffuse large B-cell lymphoma (SIRparent = 2.3), follicular lymphoma (SIRsibling = 2.3), and B-cell lymphoma not otherwise specified (NOS) (SIRsibling = 3.4). For a parental history of histopathology-specific concordant cancer, the risks were significantly increased for diffuse large B-cell lymphoma (SIR = 11.8), follicular NHL (SIR = 6.1), plasma cell myeloma (SIR = 2.5), and chronic lymphocytic leukemia (SIR = 5.9). Familial clusters for NHL seemed stronger in females and in siblings[4].
A family history of NHL or chronic lymphocytic leukemia (CLL) was associated with an increased risk of several NHL subtypes and HL, whereas familial multiple myeloma was associated with a higher risk of follicular lymphoma[5].

Fraumeni et al.[6] reported on a family with Waldenstrom macroglobulinemia, lymphocytic leukemia, Hodgkin disease, non-Hodgkin lymphoma and lung cancer. Kristinsson et al.[9] reported that first-degree relatives of patients with lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia (LPL/WM) have a 20-fold (4.1-98.4), 3.0-fold (2.0-4.4), 3.4-fold (1.7-6.6), and 5.0-fold (1.3-18.9) increased risks of developing LPL/WM, NHL, CLL, and monoclonal gammopathy of undetermined significance, respectively. No increased risk was observed in the relatives for multiple myeloma or Hodgkin's disease.

References

[1] Zhu K, Levine RS, Gu Y, Brann EA, Hall I, Caplan LS, Baum MK. Non-Hodgkin's lymphoma and family history of malignant tumors in a case-control study (United States). Cancer Causes Control 1998; 9(1):77-82.
[2] Goldin LR, Pfeiffer RM, Li X, Hemminki K. Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database. Blood 2004; 104(6):1850-4.
[3] Goldin LR, Landgren O, McMaster ML, Gridley G, Hemminki K, Li X, Mellemkjaer L, Olsen JH, Linet MS. Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples. Cancer epidemiology, biomarkers & prevention 2005; 14(10):2402-6.
[4] Altieri A, Bermejo JL, Hemminki K. Familial risk for non-Hodgkin lymphoma and other lymphoproliferative malignancies by histopathologic subtype: the Swedish Family-Cancer Database. Blood 2005; 106(2):668-72.
[5] 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.
[6] Chatterjee N, Hartge P, Cerhan JR, Cozen W, Davis S, Ishibe N, Colt J, Goldin L, Severson RK. Risk of non-Hodgkin's lymphoma and family history of lymphatic, hematologic, and other cancers. Cancer epidemiology, biomarkers & prevention 2004; 13(9):1415-21.
[7] Zhang Y, Wang R, Holford TR, Leaderer B, Zahm SH, Boyle P, Zhu Y, Qin Q, Zheng T. Family history of hematopoietic and non-hematopoietic malignancies and risk of non-Hodgkin lymphoma. Cancer causes & control 2007; 18(4):351-9.
[8] Fraumeni jr JF, Wertelecki W, Blattner WA, Jensen RD, Leventhal BG. Varied manifestations of a familial lymphoproliferative disorder. Am J Med 1975; 59(1):145-151.
[9] Kristinsson SY, Bjorkholm M, Goldin LR, McMaster ML, Turesson I, Landgren O. Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenstrom's macroglobulinemia patients: A population-based study in Sweden. Blood 2008; epub ahead of print.
[10] Brown JR, Neuberg D, Phillips K, Reynolds H, Silverstein J, Clark JC, Ash M, Thompson C, Fisher DC, Jacobsen E, LaCasce AS, Freedman AS. Prevalence of familial malignancy in a prospectively screened cohort of patients with lymphoproliferative disorders. Br J Haematol. 2008 Nov;143(3):361-8.