Leukemia is responsible for approximately 2 % of all cancers, with an incidence of about 8 per 100,000 in the UK. Acute myeloid and lymphoblastic leukemia (AML and ALL) account for about 1 % of all cancers and 1.5 % of cancer deaths. The age incidence of leukemia shows two peaks, in childhood and in the elderly. Genetic factors are not considered to have a prominent role in the pathogenesis of acute leukemia or in chronic myeloid leukemia, but have been implicated in chronic lymphocytic leukemia. Gunz et al. (1975) studied the incidence of leukemia in relatives of 909 patients with leukemia. The overall incidence of leukemia in first-degree relatives was three times higher than expected although only 2 % of patients had a first-degree relative with leukemia. Among the main subtypes of leukemia, an increased risk to relatives was most marked in chronic lymphocytic leukemia, less so in acute leukemia and absent in chronic myeloid leukemia. When familial clusters of leukemia have been reported, the type of leukemia in individual relatives is not always concordant. Familial leukemia does not necessarily indicate a genetic cause, and shared exposure to an environmental leukemogen also needs to be considered, particularly in childhood acute leukemia. In Western countries, leukemia affects approximately 1–2 % of the population. B cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia, accounting for around 30 % of all cases. The incidence rate of CLL increases logarithmically from age 35, with a median age of diagnosis at 65 years Acute myeloid and lymphoblastic leukemia (AML and ALL) account for about 1 % of all cancers and 1.5 % of cancer deaths. The age incidence of leukemia shows two peaks, in childhood and in the elderly. Genetic factors are not considered to have a prominent role in the pathogenesis of acute leukemia or chronic myeloid leukemia, but genes are being identified which do play a role in leukemia susceptibility, particularly chronic lymphocytic leukemia. Among the main subtypes of leukemia, an increased risk to relatives is most marked in chronic lymphocytic leukemia and less so in acute leukemia, but when familial clusters of leukemia have been reported, the type of leukemia in individual relatives is not always concordant. An increased relative risk of leukaemia is found in the siblings, especially twins, of cases of childhood ALL suggesting a significant contribution of genetic factors. Exposure to environmental factors may also play a part, particularly in childhood acute leukemia, where an infectious etiology has been suggested to account for increased numbers of cases in areas where there has been a sudden influx of people to a town with increased population mixing, a possible contributing cause for increased cases seen in areas around certain nuclear sites (Kinlen 2011; Bithell et al. 2008). Recent genome-wide association studies have identified loci which may contribute small alterations in relative risk of leukemia, especially CLL (Brown 2008).
Genetic disorders that have been associated with a predisposition to leukemia are shown in Table 1. Genetic disorders are ought to account for only 3 % of childhood leukemia.
Table 1. Genetic disorders associated with leukemia
|Biallelic mismatch repair gene mutations|
|Immune deficiency diseases (e.g., severe combined immunodeficiency, common variable immunodeficiency)|
|Neurofibromatosis type 1|