FaCD Online Syndrome Fact Sheet

Last updated: 20 Aug 2008

Name: Non-Hodgkin Lymphoma, Familial Clustering of

Synonym: incl.: Familial Hairy Cell Leukemia

Mode of Inheritance: multifact?

Tumor features

brain tumor
Burkitt lymphoma
gastric cancer
hairy cell leukemia
lymphoma, intestinal
non-Hodgkin lymphoma

Comment

Non-Hodgkin lymphoma (NHL) may cluster in families, often as parent/child clusters[1], and has also been reported as part of familial clustering of different types of hemato-lymphoproliferative neoplasms [2-7]. Approximately 8% of NHL patients have one first degree relative with NHL and 1% have two or more[2].

The two most frequent patterns of familial NHL are a) pre-adolescent affected sibs with (often gastrointestinal) extranodal B-cell NHL and b) adult affected siblings with nodal NHL[8]. Risk to relatives is probably not strongly dependent on the NHL histopathologic subtype[23]. The age at onset in familial cases of NHL is generally lower than in sporadic cases[8]. Wiernik et al.[9] found evidence for anticipation in familial NHL. This anticipation appeared Anticipation was found in all familial B-cell malignancies analyzed and correlated with the parental age at conception[24].

In a study of relatives of specifically children with NHL, no significant excess of NHL or any other tumors was observed[10]. However, a recent study demonstrated a significant excess of CNS tumours diagnosed at relatively young age in the relatives of children diagnosed with NHL[21].

A Swedish national study[22] reported on the effect of the gender of NHL patients on the risk to develop NHL in their relatives. In males, parental risks were approximately the same from fathers and mothers, whereas sibling risks were higher from brothers [standardized incidence ratio (SIR), 1.8; 95% confidence interval (95% CI), 1.0-2.9] than sisters (SIR, 0.9; 95% CI, 0.2-1.9). In females, parental and sibling risks were higher from same-sex relatives (SIR from mothers, 1.9; 95% CI, 1.2-2.7; SIR from sisters, 6.3; 95% CI, 4.0-9.3) than from opposite-sex relatives (SIR from fathers, 1.2; 95% CI, 0.7-1.9; SIR from brothers, 0.7; 95% CI, 0.2-1.6).

Looking at the offspring of survivors of childhood NHL has lead to the conclusion that, in this subset of cases, the proportion of a heritable form of NHL is unlikely to exceed 5 % and is likely to be much smaller[11]. It has been speculated that a subtle disturbance in cellular immune functions may play a causal role in some familial aggregations of NHL[12;13].

Thorburn et al.[14] observed that gastric NHL is, more than NHL at other sites, associated with a family history of gastric cancer. This supports the postulated role of Helicobacter Pylori in the development of both malignancies. Familial aggregation of Burkitt lymphoma, a subtype of NHL and associated with EBV infection, has been reported as well[15]. A subset of families with NHL have an intestinal location of the tumors[13;16]. Familial hairy cell leukemia, a NHL subtype, has been observed on several occasions[17-19]. Zhu et al.[20] calculated the relative risk (RR) of NHL associated with a family history of lymphoma (RR 3.0) and hematological malignancies (RR 2.3).

(See also: Hemato-Lymphoproliferative disease, familial clustering).

References

[1] 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.
[2] Pottern LM, Linet M, Blair A, Dick F, Burmeister LF, Gibson R, Schuman LM, Fraumeni jr JF. Familial cancers associated with subtypes of leukemia and non- Hodgkin's lymphoma. Leuk Res 1991; 15(5):305-314.
[3] Cartwright RA, McKinney PA, O'Brien C, Richards IDG, Roberts B, Lauder I, Darwin CM, Bernard SM, Bird CC. Non-Hodgkin's lymphoma: case control epidemiological study in Yorkshire. Leuk Res 1988; 1:81-88.
[4] Greene MH, Miller RW. Familial non-Hodgkin lymphoma: histologic diversity and relation to other cancers. Am J Med Genet 1978; 1(4):437-443.
[5] Linet MS, Pottern LM. Familial aggregation of hematopoietic malignancies and risk of non-Hodgkin's lymphoma. Cancer Res 1992; 52(19 Suppl):5468s-5473s.
[6] 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.
[7] Haim N, Cohen Y, Robinson E. Malignant lymphoma in first-degree blood relatives. Cancer 1982; 49(10):2197-2200.
[8] Lynch HT, Marcus JN, Lynch JF. Genetics of Hodgkin's and non-Hodgkin's lymphoma: a review. Cancer Invest 1992; 10(3):247-256.
[9] Wiernik PH, Wang SQ, Hu XP, Marino P, Paietta E. Age of onset evidence for anticipation in familial non-Hodgkin's lymphoma. Br J Hematol 2000; 108(1):72-79.
[10] Le Bihan C, Moutou C, Chompret A, Abel A, Poisson N, Brugieres L, Lemerle J, Bonaiti-Pellie C. Cancers in relatives of children with non-Hodgkin's lymphoma. Leuk Res 20[2], 181-186. 1996.
[11] Hawkins MM, Draper GJ, Winter DL. Cancer in the offspring of survivors of childhood leukaemia and non-Hodgkin lymphomas. Br J Cancer 1995; 71:1335-1339.
[12] Clark JW, Tucker MA, Greene MH. Clinical and laboratory observations in a lymphoma-prone family. Cancer 1987; 60(4):864-869.
[13] Maurer HS, Gotoff SP, Allen L, Bolan J. Malignant lymphoma of the small intestine in multiple family members: association with an immunologic deficiency. Cancer 1976; 37(5):2224-2231.
[14] Thorburn C, Rodriguez L, Parsonnet J. Epidemiology of gastric non-Hodgkin's lymphoma patients: parallels with Helicobacter pylori. Helicobacter 1996; 1(2):75-78.
[15] Anderson KC, Jamison DS, Peters WP, Li FP. Familial Burkitt's lymphoma. Association with altered lymphocyte subsets in family members. Am J Med 1986; 81(1):158-162.
[16] Banihashemi A, Nasr K, Hedayatee H, Mortazavee H. Familial lymphoma including a report of familial primary upper small intestinal lymphoma. Blut 1973; 26(6):363-368.
[17] Gramatovici M, Bennett JM, Hiscock JG, Grewal KS. Three cases of familial hairy cell leukemia. Am J Hematol 1993; 42(4):337-339.
[18] Ward FT, Baker J, Krishnan J, Dow N, Kjobech CH. Hairy cell leukemia in two siblings. A human leukocyte antigen- linked disease? Cancer 1990; 65(2):319-321.
[19] Casado LF, Mouleon P, Villarrubia B, del Carmen Toldedo M, del Carmen Martinez-Frejo M. Familial hairy cell leukemia: a HLA-linked disease or farmers- linked disease? Haematologica 83[8], 751-752. 1998.
[20] 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.
[21] Pang D, Alston RD, Eden TO, Birch JM. Cancer risks among relatives of children with Hodgkin and non-Hodgkin lymphoma. International journal of cancer 2008; 123(6):1407-10.
[22] Czene K, Adami HO, Chang ET. Sex- and kindred-specific familial risk of non-Hodgkin's lymphoma. Cancer epidemiology, biomarkers & prevention: 2007; 16(11):2496-9.
[23] 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.
[24] Alexandrescu DT, Wiernik PH. The influence of parental age and gender on anticipation in familial B-cell malignancies. Medical oncology 2007; 24(1):55-62.