Approximately 8–10% of patients with CLL have an inherited genetic predisposition for the disease, according to evidence from case control and cohort studies. The clinical characteristics of familial CLL do not appear to differ from those of non-familial (sporadic CLL), even by examining some of the new prognostic factors like IgVH mutation status, ZAP70 and FISH analysis of chromosomes. Studies of first-degree relatives of CLL patients show a slightly higher incidence of lymphoid malignancies (other than CLL) such as Hodgkin’s disease and Non-Hodgkin’s lymphoma. This suggests that the CLL predisposition gene(s) have a pleitropic effect; that is, the gene may also predispose to other lymphoid diseases.
Investigators in the 1940’s (Videbaek in Denmark) and 1970’s (Gunz in Australia) noticed and reported the inherited patterns of familial CLL; however, research tools to help identify the genes responsible for familial CLL have only recently become available. Several international groups are actively conducting research on the genetic predisposition of CLL. CLL Global is currently funding research in Israel and has previously funded research in the UK for this purpose.
Other studies have indicated that familial CLL is associated with an earlier age of diagnosis, but a favorable prognosis. Also, there seems to be correlation between abnormalities in chromosome 14 and familial CLL. These studies were conducted on small populations of patients. Additional studies such as the one being funded in Israel are needed to validate such findings.