Prevalence of Familial Lymphoproliferative Malignancy in a Prospectively Screened Cohort of Patients with Lymphoproliferative Disorders.

Although an inherited contribution to CLL/SLL and Hodgkin’s lymphoma (HL) is increasingly accepted, the contribution of inherited predisposition to non-Hodgkin’s lymphomas has been less well studied. The frequency of families with more than one B cell malignancy is also unknown. To begin to address these questions, we have been systematically screening all new patients seen in the Lymphoma Program at Dana-Farber Cancer Institute since December 2004, with a one-page IRB-approved self-administered family history questionnaire. Through June 30, 2006, 1509 patients have been screened, including 983 with NHL, 205 with HL and 321 with CLL/SLL. Of these, 74.5% or 1125 patients report at least one family member with cancer (95% CI 72.3%–76.7%), and 58.2% or 878 patients report at least one first degree relative (parent, sibling or child) with cancer (95% CI 55.6–60.7%). 63.5% of CLL/SLL patients, 58.4% of NHL patients and 48.7% of HD patients report a first degree family member affected with any cancer (p = 0.004, Chi-Square test). The diseases reported include: breast (220 cases), lung (152), lymphoid (127), prostate (110), and colon (101). A related lymphoproliferative disorder was reported in a first degree relative by 116 of the 1509 patients (7.7%; 95% CI 6.4–9.1%); 11 of 116 (9.5%, 95% CI 4.8–16.3 %) reported additional affected first degree relatives. An additional 53 (3.5%) patients reported a second degree relative with a related lymphoproliferative disorder. 11.2% (95% CI 9.7–12.9%) of patients therefore report a 1^st or 2^nd degree relative with a related lymphoma. Amongst patients with CLL/SLL, 8.7% (28/321) report a first degree relative who also has CLL/SLL, 4.0% (13/321) a first degree relative with NHL and 1.9% (6/321) a first degree relative with HL. Amongst patients with HL, 1.5% (3/205) report a first degree relative also with HL, 3.4% (7/205) with NHL, and 0.5% (1/205) with CLL/SLL. Of particular note is the finding that the non-Hodgkin’s lymphomas also show high rates of affected first degree relatives, with 4.5% (44/983) reporting a first degree relative also with NHL, 1.4% (14/983) with HL and 1.1% (11/983) with CLL/SLL. These results suggest that the prevalence of lymphoproliferative malignancy in first degree relatives of affected individuals is high and differs significantly by diagnosis, 14.6% (95% CI 11.0–19.0%) in CLL/SLL, 7.0% (95% CI 5.5–8.8%) in NHL and 5.4% (95% CI 2.7–9.4%) in HL (p= 0.00003, Chi-square test). Although the majority of relatives tend to have concordant histology, any B cell malignancy can be seen in these families. In order to better characterize these findings and explore the underlying biology, those families who are willing who have at least two first degree relatives with any B cell malignancy are enrolling in a prospective cohort and tissue banking study, in which detailed medical records are evaluated and germline and tumor tissue banked. Molecular experiments with the goal of elucidating the genetic mechanisms underlying these observations are ongoing.