Leukemia in children in developing world, signs and causes

There is no single known cause for any of the different types of leukemias.

Common leukemia signs and symptoms include:

• Fever or chills
• Persistent fatigue, weakness
• Frequent or severe infections
• Losing weight without trying
• Swollen lymph nodes, enlarged liver or spleen
• Easy bleeding or bruising
• Recurrent nosebleeds
• Tiny red spots in your skin (petechiae)

The few known causes, which are not generally factors within the control of the average person, account for relatively few cases. The cause for most cases of leukemia is unknown. The different leukemias likely have different causes.

• Every four minutes, someone is diagnosed with blood cancer – more than 201,870 new cases are expected this year in the United States.
• More than 327,520 Americans are living with leukemia
• Nearly 761,659 Americans are living with Hodgkin’s or non-Hodgkin’s lymphoma.
• An estimated 35,000 to 55,000 people are living with myelodysplastic syndromes in the United States
• An estimated 95,874 people are living with myeloma in the United States
• An estimated 67,870 deaths will result from blood cancer this year.
• Leukemia causes more deaths than any other cancer among children and young adults under the age of 20; however, leukemia is diagnosed 10 times more often in adults than children.
• Non-Hodgkin’s lymphoma is the 6th most common cancer in the U.S.
• Every day 148 Americans are diagnosed with leukemia and 67 lose the fight.
• Every day 221 Americans are diagnosed with lymphoma and 57 lose the fight.
• Leukemia strikes males and females of all ages and all races. It does not discriminate.
• The five-year relative survival rate for non-Hodgkin’s lymphoma and leukemia is about 8% lower for African-Americans than that of whites.
• Leukemia is the most common cancer in Hispanic children and adolescents; five-year relative survival rate is slightly lower for Hispanics than that of non-Hispanic whites.

Leukemia, like other cancers, results from mutations in the DNA. Certain mutations can trigger leukemia by activating oncogenes or deactivating tumor suppressor genes, and thereby disrupting the regulation of cell death, differentiation or division. These mutations may occur spontaneously or as a result of exposure to radiation or carcinogenic substances.

Among adults, the known causes are natural and artificial ionizing radiation, a few viruses such as human T-lymphotropic virus, and some chemicals, notably benzene and alkylating chemotherapy agents for previous malignancies. Use of tobacco is associated with a small increase in the risk of developing acute myeloid leukemia in adults. Cohort and case-control studies have linked exposure to some petrochemicals and hair dyes to the development of some forms of leukemia. Diet has very limited or no effect, although eating more vegetables may confer a small protective benefit.

Viruses have also been linked to some forms of leukemia. For example, human T-lymphotropic virus (HTLV-1) causes adult T-cell leukemia.

Some people have a genetic predisposition towards developing leukemia. This predisposition is demonstrated by family histories and twin studies. The affected people may have a single gene or multiple genes in common. In some cases, families tend to develop the same kinds of leukemia as other members; in other families, affected people may develop different forms of leukemia or related blood cancers.

In addition to these genetic issues, people with chromosomal abnormalities or certain other genetic conditions have a greater risk of leukemia. For example, people with Down syndrome have a significantly increased risk of developing forms of acute leukemia (especially acute myeloid leukemia), and Fanconi anemia is a risk factor for developing acute myeloid leukemia. Mutation in SPRED1 gene has been associated with a predisposition to childhood leukemia.

Whether or not non-ionizing radiation causes leukemia has been studied for several decades. The International Agency for Research on Cancer expert working group undertook a detailed review of all data on static and extremely low frequency electromagnetic energy, which occurs naturally and in association with the generation, transmission, and use of electrical power.They concluded that there is limited evidence that high levels of ELF magnetic (but not electric) fields might cause some cases of childhood leukemia. No evidence for a relationship to leukemia or another form of malignancy in adults has been demonstrated. Since exposure to such levels of ELFs is relatively uncommon, the World Health Organization concludes that ELF exposure, if later proven to be causative, would account for just 100 to 2400 cases worldwide each year, representing 0.2 to 4.9% of the total incidence of childhood leukemia for that year (about 0.03 to 0.9% of all leukemias).

A few cases of maternal-fetal transmission (a baby acquires leukemia because its mother had leukemia during the pregnancy) have been reported.

According to a study conducted at the Center for Research in Epidemiology and Population Health in France, children born to mothers who use fertility drugs to induce ovulation are more than twice as likely to develop leukemia during their childhoods than other children.

Leukemia is a cancer of the tissues that produce blood cells, resulting in abnormal blood cells.  Leukemia appears to be related to damage to chromosomes or genes.  The damage disrupts the process by which blood cells achieve their final and functional form.

Leukemia is the most common kind of cancer in children

Leukemia also causes more deaths than any other form of cancer in children.  Fortunately, improved treatment methods have greatly reduced deaths from leukemia.

Leukemia rates are higher for white children than black children.

There are several forms of leukemia, two of which are particularly important in children.  These are usually known as ALL and AML.

Acute lymphoblastic leukemia (ALL) is the most common form in children and represents 78% of cases of leukemia.   (ALL is also called acute lymphocytic leukemia.)  From 1991 to 1994, the incidence rate was 59 cases per million children under five.   ALL reaches its greatest frequency in children between 2 and 6, with a peak of more than 80 cases per million children per year at ages 3 to 4.  Rates then decline to age 20.  Scientists believe that this pattern means that two genetic changes are needed to cause the disease and that one occurs before a child is born.

ALL increased about 1% per year between 1977 and 1995, though some of this change may result from changes in the groups that are tracked for cancer . However, many scientists believe that this change represents a genuine increase in the frequency of the disease that could be caused by environmental factors.

Acute non-lymphocytic leukemia is the second most common form of leukemia in children and represents 19% of cases.  It is also called acute myelogenous leukemia (AML).  It is the form of leukemia most commonly diagnosed in children less than one year old.   Rates are higher at ages 1-3 and in late adolescence .

Unlike ALL, the rates for AML do not appear to have increased since 1975 .

Known and Suspected Causes of Leukemia

Both pre-natal and post-natal exposure to ionizing radiation (particularly X rays) can cause leukemia in children.  Pre-natal exposure to X rays has been greatly reduced with the adoption of ultrasound for screening in pregnant women.

Several studies link pesticide exposure by both parents and children to leukemia.  The pattern of disease suggests that some damage to chromosomes may occur before the child is born (3).  Children born to parents employed in certain occupations that have chemical exposures are more likely to have leukemia . Chemicals, specifically including benzene, have been shown to cause leukemia in adults.

A recent review of 48 epidemiological studies concluded that the strongest evidence for a relationship between a parent’s exposure to chemicals other than pesticides and childhood leukemia was for solvents, paints, and employment in motor vehicle-related occupations .

These studies tend to look at the occupation of fathers more often than those of mothers, despite the fact that exposures of mothers are likely to be at least as important.  For occupations of the mothers, the review concluded that the most significant were employment in personal services industries, in metal processing, and in textiles.   All three categories had significantly elevated risks.  For occupations of fathers, employment in painting led to increased risk of leukemia in a child..

Some studies show that exposure to electric and magnetic fields (EMFs) is associated with increased risk of leukemia.

There has been some evidence for an association between leukemia and smoking by parents, though the largest study performed to date did not find that smoking by parents, either before birth or afterwards, increased risk of ALL or AML in children .

IONIZING RADIATION

Ionizing radiation is considered a “known” cause of childhood leukemia.  Follow-up studies of people who survived the detonation of atomic bombs at Hiroshima and Nagasaki found that the risk of leukemia was higher for those exposed to radiation.  The risk is also higher for those exposed at an earlier age .  Radiation from nuclear power plants is a known cause for both kinds of leukemia .  A recent study found that exposure to X rays after birth also increased the risk of leukemia.  Infants receiving diagnostic X rays had 60% more leukemia than other children .

PESTICIDES

Several studies have linked leukemia to pesticides.  Two recent reviews concluded that pesticide exposure may be a cause of leukemia (10)(11). These reviews report that most, though not all, studies find leukemia was more likely in children whose fathers were exposed to pesticides at work than other children.   Risks for children are often reported to be greater than risks for adults (12).

• One large recent study of 491 children with ALL found that risk was increased by home use of some kinds of pesticides and by use of multiple different pesticides. Herbicide use during pregnancy was associated with a 50% increase in risk.  Use of insecticides in the home was associated with increased risk of ALL, and frequent use was associated with higher risk.  Use of some garden products also seemed to increase risk.  The heightened risk was associated with use of multiple products (13).
• A study of childhood leukemia cases in Shanghai found a more than threefold increase in risk for children whose mothers were exposed to pesticides at work (14).
• A study of children under 15 in the Denver area reported that use of pest strips was associated with higher risks of leukemia (15).
• A study of children in the US found that AML risk was increased when either parent was exposed to pesticides or when the child was exposed to pesticides after birth (16).
• In 1989, the Children’s Cancer Study Group reported that, among families of 204 children with AML, children whose fathers worked with pesticides for more than 1000 days had nearly three times the risk of other children. The risk was greater for children under the age of 6.    Children regularly exposed to pesticides in the household had 3.5 times greater risk of leukemia than those not exposed (17).
• In a 1987 National Cancer Institute study, the risk of childhood leukemia increased nearly four times when pesticides were used within the house at least once per week. The risk increased more than six times when garden pesticides were used at least once per month (18).
• Children of fathers with jobs including pesticide exposure had a 2.7 times higher risk of leukemia when compared to controls (17).
• A small study in the Netherlands reported increased risk of leukemia in children who were exposed to pesticides directly or whose fathers were exposed at work (19).
• An increased risk was found for children whose parents used pesticides in the home (OR = 3.8, P = .004) or garden (OR = 6.5, P = .007) or who burned incense in the home (OR = 2.7, P = .007). The risk was greater for frequent use (18).

SOLVENTS

• A 1998 review concluded that the evidence for an association between childhood leukemia and paternal exposure to solvents is “quite strong.” Chemicals where risks are elevated include solvents in general, chlorinated solvents, benzene, carbon tetrachloride, and trichloroethylene (TCE) .
• A study of nearly 2,000 children found that the risk of acute lymphoblastic leukemia (ALL) was increased if the children’s mothers were exposed to solvents, paints, or thinners before conception or during pregnancy or to plastics after birth. The father’s exposure to plastics before conception was associated with greater risk.  This study reported that the timing of exposure was an important factor (20).
• A study of children in the US found that the father’s exposure to petroleum products increased the risk of AML (16). Petroleum products usually contain benzene.
• An earlier study had found that children born to fathers with exposure to solvents, petroleum products, plastics or lead were more likely to have AML than other children (17). For solvents, the excess risk was substantial. The same study found that children born to mothers with exposure to metal dusts, pigments and paints at work were more likely to have AML.
• A case-control study of 123 children 10 and under in Los Angeles County looked at specific occupational and home exposures and found an increased risk of leukemia for children whose fathers were exposed at work after the birth of the child to chlorinated solvents {odds ratio (OR) = 3.5, p = .01}. Risk of leukemia was related to mothers’ employment in personal service industries (OR = 2.7, p = .04) but not to specified occupational exposures (18).
• A Scottish study found greatly increased risk of leukemia for children born to fathers who had exposure to benzene (21).
• A study of children in Shanghai reported increased ALL in children whose mothers were employed in the chemical industry during pregnancy, increased AML in children whose mothers were exposed to benzene and increased AML and ALL to children whose mothers were exposed to gasoline (14). Also children born to women employed in metal processing were more likely to have AML.
• A study in the Netherlands found that mothers who were exposed to hydrocarbons at work or certain other chemicals in the year before the birth of their child were more likely to have a child with ALL (22).
• A study in New York found that children born to fathers who worked in motor vehicle-related jobs were more than twice as likely to have leukemia (23).

EMFs – Electric and Magnetic Fields

Evidence about whether Electric and Magnetic Fields (EMFs)contribute to leukemia in children is contradictory, with some studies finding an effect and others not finding an effect.  However, there are many ways to measure these fields (24), and the various approaches do not correlate in all cases (25).    Some of the contradictory results could be due to differences in methods of measuring the EMFs.  Also, as is true with other possible causes, there may be a specific time period when children are most susceptible, studies do not necessarily identify the relevant time period.

• More positive results are found when EMFs are measured according to “wire codes,” which are classifications based on how wiring is configured (26) than when EMFs are measured directly (27).
• Several studies have found that exposure to EMFs increases risk of leukemia for children (28). One study found that children living near high voltage power installations were more likely to be found to have leukemia than other children.  However, other studies have failed to find any link.
• A 1995 review of several studies reported a link between EMF exposure and increased leukemia that cannot be readily explained by errors in the studies.
• One recent study found that risk of leukemia was elevated when exposure to EMFs was consistent over the term of the pregnancy and in cases where the design of the water system in the home led to “ground currents” from connections between plumbing pipes and the grounding for the electricity.
• A large study in Britain found no association between exposure to EMFs and leukemia in 3,838 children. A study in Los Angeles that looked at combined measures of EMF found increased risk of leukemia to be associated with increased EMF exposure.
• A first study of exposures of parents to EMFs at work before their children were born found that fathers with high exposures were more likely to have children who got leukemia. This study had several good design elements that avoided problems with recall of exposures by parents.

Radon

Radon is a naturally occurring radioactive gas that gets into homes from materials underneath houses, such as soil or rocks, or from water piped into the houses.  Two studies have investigated whether radon exposure is related to ALL but have not found any relationship.  Both of these studies were limited in the conclusions that they could draw because participation rates were low.  One earlier study reported an association between levels of radon in geographic areas and increased risk of childhood leukemia.

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