Leukemia

Leukemia is the general term that includes a group of different cancers that occur in the blood forming organs and result in the formation of abnormal amounts and types of white blood cells in the blood and bone marrow.  Individuals with leukemia generally maintain abnormally high amounts of leukocytes or white blood cells in their blood.  This condition results in an individual’s inability to maintain certain body functions, particularly a person’s ability to combat infection.

In 2005, leukemia is expected to affect approximately 34,810 individuals (19,640 males and 15,170 females) in the United States, resulting in 22,570 deaths.  In Massachusetts, approximately 770 individuals will be diagnosed with the disease in 2005, representing more than 2% of all cancer diagnoses.  There are four major types of leukemia: acute lymphoid leukemia (ALL), acute myeloid leukemia (AML), chronic lymphoid leukemia (CLL), and chronic myeloid leukemia (CML).  There are also a few rare types, such as hairy cell leukemia.  In adults, the most common types are AML and CLL.  Leukemia is the most common type of childhood cancer, accounting for about 30% of all cancers diagnosed in children.  The majority of these cases are of the ALL type (ACS, 2005).

While ALL occurs predominantly among children (peaking between ages 2 and 3 years), an elevation in incidence is also seen among older individuals.  The increase in incidence among older individuals begins at approximately 40-50 years of age, peaking at about age 85 (Linet and Cartwright, 1996).  ALL is more common among whites than African Americans and among males than females (Weinstein and Tarbell, 1997).  Exposure to high-dose radiation (e.g., by survivors of atomic bomb blasts or nuclear reactor accidents) is a known environmental risk factor associated with the development of ALL (Scheinberg et al., 1997).  Significant radiation exposure (e.g., diagnostic x-rays) before birth may carry up to a 5-fold increased risk of developing ALL (ACS 2000b).  However, few studies report an increased risk of leukemia associated with residing in proximity to nuclear plants or occupational exposure to low-dose radiation (Linet and Cartwright, 1996; Scheinberg et al., 1997).  It is unclear whether exposure to electromagnetic fields (EMF) plays a role in the development of ALL, however, most studies to date have found little or no risk (ACS 2000b).

Few other risk factors for ALL have been identified.  There is evidence that genetics may play an important role in the development of this leukemia type.  Studies indicate that siblings of twins who develop leukemia are at an increased risk of developing the disease.  Children with Down’s syndrome are 10 to 20 times more likely to develop acute leukemia (Weinstein and Tarbell, 1997).  In addition, other genetic diseases, such as Li-Fraumeni syndrome and Klinefelter’s syndrome, are associated with an increased risk of developing leukemia.  Patients receiving medication that suppresses the immune system (e.g., organ transplant patients) may be more likely to develop ALL (ACS 2000b).  ALL has not been definitively linked to chemical exposure, however, childhood ALL may be associated with maternal occupational exposure to pesticides during pregnancy (Infante-Rivard et al., 1999).  Certain rare types of adult ALL are caused by human T-cell leukemia/lymphoma virus-I (HTLV-I) (ACS, 2000a).  Some reports have linked other viruses with various types of leukemia, including Epstein-Barr virus and hepatitis B virus.  Still others propose that leukemia may develop as a response to viral infection.  However, no specific virus has been identified as related to ALL (Linet and Cartwright, 1996).  Recent reports also suggest an infectious etiology for some childhood ALL cases, although a specific viral agent has not been identified and findings from studies exploring contact among children in day-care do not support this hypothesis (Greaves MF, 1997; Kinlen and Balkwill, 2001; Rosenbaum et al., 2000).

Although AML can occur in children (usually during the first two years of life), AML is the most common leukemia among adults, with an average age at diagnosis of 65 years (ACS, 2000a and 2000b).  This type of leukemia is more common among males than among females but affects African Americans and whites at similar rates (Scheinberg et al., 1997).  High-dose radiation exposure (e.g., by survivors of atomic bomb blasts or nuclear reactor accidents), long-term occupational exposure to benzene, and exposure to certain chemotherapy drugs, especially alkylating agents (e.g., mechlorethamine, cyclophosphamide), have been associated with an increased risk of developing AML among both children and adults (ACS, 2000a and 2000b; Linet and Cartwright, 1996).  The development of childhood AML is suspected to be related to parental exposure to pesticides and other chemicals, although findings are inconsistent (Linet and Cartwright, 1996).  Recent studies have suggested a link between electromagnetic field (EMF) exposure (e.g., from power lines) and leukemia (Minder and Pfluger, 2001; Schuz et al., 2001).  However, there is conflicting evidence regarding EMF exposure and leukemia and it is clear that most cases are not related to EMF (ACS, 2000a; Kleinerman et al., 2000).

Other possible risk factors related to the development of AML include cigarette smoking and genetic disorders.  It is estimated that approximately one-fifth of cases of AML are caused by smoking (Scheinberg et al., 1997).  Also, a small number of AML cases can be attributed to rare inherited disorders.  These include Down’s syndrome in children, Fanconi’s anemia, Wiskott-Aldrich syndrome, Bloom’s syndrome, Li-Fraumeni syndrome, and ataxia telangiectasia (ACS, 2000a and 2000b).  Recently, scientists have suggested that a mutation in a gene responsible for the deactivation of certain toxic metabolites may have the ability to increase the risk of acute myeloid leukemia in adults.  However, further research is necessary in order to confirm the findings of this study (Smith et al., 2001). 

CLL is chiefly an adult disease; the average age at diagnosis is about 70 years (ACS 1999).  Twice as many men as women are affected by this type of leukemia (Deisseroth et al., 1997).  While genetics and diseases of the immune system have been suggested as playing a role in the development of CLL, high-dose radiation and benzene exposure have not (ACS, 1999; Weinstein and Tarbell, 1997).  It is thought that individuals with a family history of CLL are two to four times as likely to develop the disease.  Some studies have identified an increased risk of developing CLL (as well as ALL, AML, and CML) among farmers due to long-term exposure to herbicides and/or pesticides (Linet and Cartwright, 1996).  In addition, many researchers believe that cigarette smoking plays a role in some chronic leukemias.  The role of EMF in the development of chronic leukemia remains controversial (ACS, 1999).  Although viruses have been implicated in the etiology of other leukemias, there is no evidence that viruses cause CLL (Deisseroth et al., 1997).

Of all the leukemias, CML is among the least understood.  While this disease can occur at any age, CML is extremely rare in children (about 2% of leukemias in children) and the average age of diagnosis is 40 to 50 years (ACS 1999).  Incidence rates are higher in males than in females, but unlike the other leukemia types, rates are higher in blacks than in whites in the U.S. (Linet and Cartwright, 1996).  High-dose radiation exposure may increase the risk of developing CML (ACS, 1999).  Finally, CML has been associated with chromosome abnormalities such as the Philadelphia chromosome (Weinstein and Tarbell, 1997).

References

American Cancer Society. 2005. Cancer Facts & Figures 2005.  Atlanta: American Cancer Society, Inc.

American Cancer Society. 1999. Leukemia – Adult Chronic. Available at: http://www3.cancer.org/cancerinfo/.

American Cancer Society. 2000a. Leukemia – Adult Acute. Available at: http://www3.cancer.org/cancerinfo/.

American Cancer Society. 2000b. Leukemia – Children’s. Available at: http://www3.cancer.org/cancerinfo/.

Deisseroth AB, Kantarjian H, Andreeff M, Talpaz M, Keating MJ, Khouri I, Champlin RB. Chronic leukemias. In: Cancer: Principles and Practice of Oncology, Fifth Edition, edited by Devita V, Hellman S, Rosenberg S.  Lippincott-Raven Publishers, Philadelphia 1997. P. 1271-1297.

Greaves MF. 1997. Aetiology of acute leukaemia. Lancet 349:344-9.

Infante-Rivard C, Labuda D, Krajinovic M, Sinnett D. 1999. Risk of childhood leukemia: associated with exposure to pesticides and with gene polymorphisms. Epidemiology 10:481-7.

Kinlen LJ, Balkwill A. 2001. Infective cause of childhood leukaemia and wartime population mixing in Orkney and Shetland, UK. Lancet 357:858.

Kleinerman RA, Kaune WT, Hatch EE, Wacholder S, Linet MS, Robison LL, Niwa S, Tarone RE. 2000. Are children living near high-voltage power lines at increased risk of acute lymphoblastic leukemia? Am J Epidemiol 151(5):512-5.

Linet MS, Cartwright RA. 1996. The Leukemias. In: Cancer Epidemiology and Prevention. 2nd Ed, edited by Schottenfeld D,  Fraumeni. JF. New York:  Oxford University Press: 1996.

Minder CE, Pfluger DH. 2001. Leukemia, brain tumors, and exposure to extremely low frequency electromagnetic fields in Swiss railway employees. Am J Epidemiol 153(9):825-35.

Rosenbaum PF, Buck GM, Brecher ML. 2000. Early child-care and preschool experiences and the risk of childhood acute lymphoblastic leukemia. Am J Epidemiol 152(12):1136-44.

Scheinberg DA, Maslak P, Weiss M. Acute leukemias. In: Cancer: Principles and Practice of Oncology, Fifth Edition, edited by Devita V, Hellman S, Rosenberg S.  Lippincott-Raven Publishers, Philadelphia 1997. P. 1271-1297.

Schuz J, Grigat JP, Brinkmann K, Michaelis J. 2001. Residential magnetic fields as a risk factor for childhood acute leukaemia: results from a German population-based case-control study. Int J Cancer 91(5):728-35.

Smith MT, Wang Y, Kane E, Rollinson S, Wiemels JL, Roman E, Roddam P, Cartwright R, Morgan G. 2001. Low NAD(P)H:quinone oxidoreductase 1 activity is associated with increased risk of acute leukemia in adults. Blood 97(5):1422-6.

Weinstein HJ, Tarbell NJ. Leukemias and lymphomas of childhood. In: Cancer: Principles and Practice of Oncology, Fifth Edition, edited by Devita V, Hellman S, Rosenberg S.  Lippincott-Raven Publishers, Philadelphia 1997. P. 1271-1297.