Familial chronic lymphocytic leukaemia

Abstract

Approximately 1.3% of males and 1% of females in Europe and North America develop leukaemia. CLL is the most common of its subtypes, constituting about 30% of all cases. Its incidence rate increases logarithmically from age 35 and has a median age of onset of 64 years. No single cytogenetic abnormality or gene mutation is found in all CLL cases. However, activation of each of the oncogenes BCL1, BCL2 and BCL3 has been reported in some cases after detection of cytogenetic abnormalities, as has mutation in tumour suppressor genes including those associated with the mutator phenotype and p53 . A putative tumour suppressor locus has been identified on chromosome 13q14. A number of case-control and cohort studies have examined the cancer risks associated with a family history of lymphoproliferative disorders, including CLL (Table 1). These studies showed an elevated risk of lymphoproliferative disorders in relatives. Although no study has systematically examined the incidence of leukaemia by specific subtype in cases and relatives, there is evidence suggesting that the familial risk of leukaemia is greater than the risk of all lymphoproliferative disorders. In the cohort study reported by Goldgar et al using the Utah population database, a 6-fold increase in risk was seen in relatives of patients with lymphocytic leukaemia. This database comprises over 1.4 million records on a population with normal levels of inbreeding that is genetically representative of a Northern European population.