Information about the prevention of cancer and the science of screening appropriate individuals at high-risk of developing cancer is gaining interest. Physicians and individuals alike recognize that the best “treatment” of cancer is preventing its occurrence in the first place or detecting it early when it may be most treatable.
Acute lymphoblastic leukemia (ALL) is the most common form of leukemia in children. At this time, we do not know what causes childhood ALL. Researchers are trying to solve this problem. Scientists know that ALL occurs in males more often than in females and in Caucasians more often than in African-Americans. However, they cannot explain why one person gets ALL and another does not. By learning what causes this disease, researchers hope to better understand how to prevent and treat it.
The chance of an individual developing cancer depends on both genetic and non-genetic factors. A genetic factor is an inherited, unchangeable trait, while a non-genetic factor is a variable in a person’s environment, which can often be changed. Non-genetic factors may include diet, exercise, or exposure to other substances present in our surroundings. These non-genetic factors are often referred to as environmental factors. Some non-genetic factors play a role in facilitating the process of healthy cells turning cancerous (e.g. the correlation between smoking and lung cancer) while other cancers have no known environmental correlation but are known to have a genetic predisposition, meaning a person may be at higher risk for a certain cancer if a family member has that type of cancer.
Heredity and Genetic Factors
It is very likely that identical twins who develop ALL in the first year of life will both develop the disease. However, after the first year of life, the identical twin of a patient with ALL only has a slightly increased risk of developing ALL when compared to the general population. This is also true for other siblings. This strongly suggests that environmental factors are much more important than genetic factors for the development of childhood ALL. It is a scientific mystery as to why only one of a pair of identical twins will develop ALL since the genetics are identical and environmental exposures are similar, if not the same.
One congenital condition, Down syndrome, is associated with an increased likelihood of ALL and acute myeloid leukemia.
Environmental or Non-Genetic Factors
The fact that only one of a pair of identical twins usually develops ALL suggests that finding the specific cause for ALL will be difficult if not impossible. Even by studying large numbers of people all over the world, researchers have not found significant risk factors that increase a person’s chance of developing ALL. Some researchers theorize that childhood ALL is associated with viral infections which later lead to leukemia in some unknown way.
Folic Acid: There have been several studies that suggested maternal use of folic acid is associated with a lower incidence of childhood ALL.1 However, not all studies have confirmed these observations.2
Anemia: An increased incidence of childhood ALL has been observed in children whose mothers are anemic.3 Maternal iron supplementation in iron deficient mothers may decrease the risk of her child developing ALL.
Parental Drug Use: Researchers affiliated with the Children’s Oncology Group have determined that medication use by parents during conception and pregnancy can affect the incidence of ALL in childhood.4 In this study, the researchers evaluated vitamin and iron supplements in the mother and mind-altering drugs including amphetamines and marijuana in both parents. The data indicated, as in other studies, that vitamin and iron supplementation by the mother during pregnancy was associated with a 20-30% reduction in the incidence of childhood ALL. Data also indicated that the use of amphetamines, diet pills, or mind-altering drugs by either the mother or the father increased the incidence of ALL. There was a two-fold or more increase in the incidence of ALL when both parents reported using these drugs. Maternal use of antihistamines or allergic remedies and parental use of mind-altering drugs were strongly associated with an increased incidence of infant ALL.
Prenatal Radiation Exposure: Prenatal radiation exposure is considered a risk factor for developing childhood ALL and is generally avoided unless the X-ray study is absolutely needed.5 There is very little data on the effects of radiation from modern CAT scans and MRIs during pregnancy on the subsequent development of childhood ALL.
Radon: High levels of domestic exposure to radon, a naturally occurring radioactive gas, have been associated with an increased incidence of childhood ALL.6 Radon accumulates in poorly ventilated houses and is most notable as a risk factor for lung cancer.
Electromagnetic Fields (EMF): A recent review suggests that high exposure to very high levels of extremely low frequency EMF could increase the risk of childhood leukemia by a factor of 2.7 However, the authors of this study pointed out that less than 1% of children are exposed to very high levels of EMF.
Viruses and Acute Lymphoblastic Leukemia: Scientists have identified a virus that seems to increase the risk for one adult type of ALL, but this is a very uncommon type of leukemia. Scientists throughout the world continue to study viruses and other possible risk factors for ALL. The current hypothesis is that a viral infection could result in predisposition to a second unknown factor, which triggers ALL.
Exposure to Infection: Previous studies have suggested that children exposed to a wide range of pathogens early in life have a decreased incidence of childhood ALL. Researchers affiliated with the United Kingdom Childhood Cancer Study (UKCCS) have confirmed these observations.8 They used daycare attendance in the first year of life as a measure of exposure to a wide range of pathogens. These researchers found that any activity outside the home during the first year of life was associated with a decreased incidence of ALL. Formal day care attendance and especially attendance during the first three months of life was associated with the lowest risk of ALL. The magnitude of this risk reduction was in the 40-50% range. There was also a reduction in the incidence of all other childhood cancers, but the magnitude of this effect was less than for ALL. The authors of the report concluded that the most likely explanation of the results is a protective effect of exposure to common infections. They pointed out that similar observations have been made concerning type 1 diabetes and allergies. They suggest that these data support what is becoming a growing consensus that child health is improved with early infection exposure. These data may also explain why the incidence of childhood ALL is lower in undeveloped countries.
Prevention of Acute Lymphoblastic Leukemia
Acute lymphoblastic leukemia cannot be prevented since we do not know the cause. Nevertheless, it would appear that pregnant women would be prudent to take adequate quantities of folic acid and iron supplementation as needed to avoid anemia. Pregnant women should also prudently avoid any drugs that are not absolutely necessary, especially alcohol, tobacco, marijuana, mind-altering drugs, and stimulants such as amphetamines. Diagnostic X-ray studies during pregnancy should be limited to what is absolutely necessary. Although many of these factors are not clearly associated with an increased incidence of childhood ALL, they can cause other problems in the fetus. The data on early infections and risk of ALL would suggest that early exposure to environmental pathogens could be of benefit in reducing several diseases.
Screening and Early Diagnosis of Acute Lymphoblastic Leukemia
For many types of cancer, progress in the areas of cancer screening and treatment has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have any symptoms of a cancer but are at high risk for that cancer. When individuals are at high risk for a type of cancer, this means that they have certain characteristics or exposures, called risk factors that make them more likely to develop that type of cancer than those who do not have these risk factors. The risk factors are different for different types of cancer. An awareness of these risk factors is important because 1) some risk factors can be changed (such as smoking or dietary intake), thus decreasing the risk for developing the associated cancer; and 2) persons who are at high risk for developing a cancer can often undergo regular screening measures that are recommended for that cancer type. Researchers continue to study which characteristics or exposures are associated with an increased risk for various cancers, allowing for the use of more effective prevention, early detection, and treatment strategies.
Acute lymphoblastic leukemia is usually diagnosed because patients have signs and symptoms of leukemia including fatigue, weight loss, bleeding, easy bruising or unexplained infections. Occasionally, the diagnosis is made on routine physical examination by performing a white blood count, platelet count and red blood cell determination.
In order for screening to be effective, patients at risk need to be identifiable. This is not currently possible, with the exception of screening those who may have one of a few genetic diseases, such as Down syndrome. It has also not been shown that early diagnosis of ALL improves chances of survival more than later, symptomatic detection.
1 Thompson JR, Gerald PF, Willoughby ML et al. Maternal folate supplementation in pregnancy and protection against acute lymphoblastic leukemia. Lancet 2001;358:1935-1940.
2 Dockerty JD, Herbison P, Skegg DC, et al. Vitamin and mineral supplementation and the risk of childhood acute lymphoblastic leukemia: a case control study. BMC Public Health 2007;7:136.
3 Roman E, Simpson J, Ansell P. et al. Perinatal and reproductive factors: a report on haematological malignancies from the UKCCS. European Journal of Cancer 2005;41:749-759.
4 Wen W, Ou Shu XO, Potter JD, et al. Parental medication use and risk of childhood acute lymphoblastic leukemia. Cancer 2002;95:1786-1794.
5 Wakeford R and Little M. Risk coefficients for childhood cancer after intrauterine irradiation: a review. International Journal of Radiation Biology 2003;79:293-309.
6 Raaschou-Neilsen O, Andersen CE, Andersen HP, et al. Domestic radon and childhood cancer in Denmark. Epidemiology 2008; 19(4):536-543.
7 Ahlbom IC, Cardis E, Green A, Review of the epidemiologic literature on EMF and health. Environmental Health Perspective 2001;109:911-933
8 Gilham C, Peto J, Simpson J, et al. Day care in infancy and risk of childhood acute lymphoblastic leukemia: findings from UK case-control study. British Medical Journal. Published online April 22, 2005.
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