What are the factors that cause the cancer /risk factors?
Many people try to determine what gave cancer a foothold, sometimes from intellectual curiosity and sometimes from a determination not to suffer a relapse. Only two causes of NHL have been proven, but there are several circumstances and substances which are suspected to play a part in the development of at least some NHLs. It's probable that you'll never know the exact cause of your illness, but the following sections offer possible explanations.
Two known viral causes of NHL
Two viruses have been linked to some cases of NHL:
· Epstein-Barr virus (EBV).
· Human T-cell lymphoma/leukemia virus (HTLV-I).
People who have previously been exposed to the Epstein Barr virus (which causes glandular fever) or the human T-cell lymphoma virus 1 (HTLV1) may have a slightly increased risk of developing lymphoma.
It is known with certainty that 1-2 percent of those who are immunosuppressed shortly after solid organ transplantation, or owing to HIV/AIDS, develop NHL that is linked to the presence of Epstein-Barr virus, a human herpes virus present in more than 90 percent of humans by adulthood. These virally induced NHLs can regress if immunosuppression is reduced, and clearly are linked to the suppression of functioning white blood T-cells. Unlike other cancers, which are monoclonal, indicating growth from only one precursor cell, these NHLs can be polyclonal, more closely resembling a process of white blood cell growth similar to that following infection.
It is also known that those who are infected early in life with the human T-cell lymphoma/leukemia virus I (HTLV-I) have about a 3 percent chance of developing aggressive T-cell lymphomas or leukemias, as well as other health problems such as illnesses of the central nervous system.[13]
Unproven, possible causes of NHL
As mentioned earlier, there are a number of possible causes of NHL that have yet to be proven scientifically. Some have stronger evidence than others, and some have produced conflicting results in studies, but all have at least some validity.
(A) Pesticides, including Agent Orange
Pesticides, consisting of insecticides and herbicides, have been examined as a possible cause of NHL. As home use of pesticides contributes five to ten times more contaminant to the environment than does farming, we are wise to continue to study this possibility, to protect ourselves if we must use pesticides, and to use only the safest products available. Some or most pesticides can be absorbed directly through the skin and often are inadvertently inhaled, thus making questionable the safety studies performed by the industry which rely on oral dosing to prove that some pesticides do not cause cancer in laboratory animals.
(B) Hair dye use
Some studies have shown that those who use dark hair dye are more likely than the general population to develop NHL, but other studies have not supported this.
(C) Foods
Some studies have shown that those who drink a great deal of milk are more likely than the general population to develop NHL, but not all studies examining the connection between NHL and milk consumption have supported this conclusion.
High consumption of meat has been linked in some studies to an increased risk of NHL, but other studies show no connection.
On the other hand, studies have shown that those eating a diet rich in carotenes, vitamin C, carrots, dark green vegetables, citrus fruits, whole-grain breads, and pasta have a lower incidence of NHL.
(D) Drug, alcohol, and tobacco use
Amphetamines, Quaaludes, lysergic acid diethylamide (LSD), and especially cocaine use have been linked to the development of NHL in men by one recent study, as was prescription amphetamine use in a second recent study that did not specify gender. Other studies suggest that the long-term illegal use of narcotic drugs may also increase NHL incidence. More research is needed to confirm these associations.
Phenytoin, or Dilantin, used for control of seizures, has been shown to increase the rate of a lymphoproliferative syndrome that resembles NHL.
Alcohol and tobacco use have been shown by several studies to have no effect on the rate of NHL.
(E) Other infectious suspects
Two known viral causes of NHL, Epstein-Barr virus and HTLV-I, are implicated in some cases of NHL. Other infectious agents are suspected as well.
The higher incidence of NHL among slaughterhouse workers and farmer-breeders also hints at possibly a third, as yet unknown, viral association.
Those who have chronic liver disease caused by infection with the hepatitis C viruses early in life are more likely to develop primary splenic and liver (hepatic) NHL.
AIDS-associated NHL, usually an aggressive NHL with a diffuse appearance, has in some cases been linked to human herpes virus 8 (HHV-8) based on traces of viral protein found within the tumor, but less research on this link has been done than on that between Epstein-Barr virus and NHL in the immune-suppressed. Nonetheless, HHV-8 is a reasonable suspect, as it's known to cause Kaposi's sarcoma, a skin tumor, among those with AIDS, and also has been linked to aggressive body-cavity or primary-effusion NHL.
In recent years, it has become clear that some cases of gastric lymphoma of the mucosa-associated lymphoid tissue (MALT) is linked to infections of Helicobacter pylori, a bacterium capable of surviving in the acidic stomach environment. When H. pyloriistreated with antibiotics, in many cases the lymphoma recedes. Not all grades of gastric MALT lymphoma recede when H. pylori is treated with antibiotics, however. The effect of antibiotic treatment on other MALT lymphomas has not been closely studied to date, but a few studies have shown a possible link between H. pylori and MALT lymphoma in the lungs.
(F) Genetic predisposition
Many people diagnosed with NHL become concerned that their siblings or children also may face a risk of developing NHL. Unfortunately, the familial aspect of NHL remains unclear. For example, a family history of leukemia or lymphoma increases the risk for NHL to two to three times the risk of the general population, but cases occurring within the same family account for less than 5 percent of all cases.
It is most important to bear in mind that, as the cause of NHL is still the subject of research, "familial" may imply an inherited genetic error, a shared exposure to an infectious cause, or a shared lifestyle. That is, the risk might come from inherited genes that predispose someone to develop NHL, just as there are genes that affect other aspects of our body's appearance and function. The risk might be that family members tend to be exposed to the same viruses or bacteria. Or the risk might turn out to be that families that live together are drinking the same water or living next to the same toxic dump..
Predisposition to a certain illness can arise when there are natural variations in genes. Such multiple versions of genes are called alleles, and many such exist. For example, it is highly likely that you have two alleles for every gene in your body, having inherited one allele for each from your father and one from your mother.
Genes are translated into proteins to accomplish their metabolic goals; proteins always fold into a specific shape dictated by their chemical makeup. Even a small difference in only one location of a gene can cause a protein string to fold differently, and this final shape dictates how or if the protein will function. Proteins that are created from the differing alleles, then, may have different structures and shapes, and may behave differently in metabolic reactions. Thus, researchers have begun to note that those who have specific versions of the HLA-DR gene on chromosome 6, for example-a gene controlling some of the behavior of white blood cells--appear in some cases to be more likely to develop certain diseases.
In fact, throughout this discussion of potentially causative factors, you can see that most of these factors could be explained using predisposition, heritability, or infection as the scientific model.
(G) Blood transfusions
There is a low but present risk of developing NHL following blood transfusions, especially among the elderly. This might indicate an infectious process or a derangement of the regulatory efforts of the immune system when coping with alien blood products.
(H) Occupational risk
An increased incidence of NHL has been noted among those in the following professions: farming, livestock breeding, rubber workers, chemists, chemical workers, dry cleaners, metal workers, funeral directors and embalmers, petroleum refinery workers, printing workers, those exposed to ethylene oxide, beauticians/cosmetologists, woodworkers (including those in sawmills and pulp mills), and those exposed to certain chemicals such as ammonia or to organic solvents such as benzene.
(I) Risk associated with other illness
A small increased risk is seen among those with asthma, allergies, arthritis, rheumatic fever, nontropical celiac sprue, tuberculosis, and infectious mononucleosis. Epstein-Barr virus is considered to be the cause of infectious mononucleosis. Asthma, allergies, nontropical celiac disease, and some forms of arthritis are illnesses caused by the inappropriate or misdirected activity of white blood cells. As NHL also is a disorder of white blood cell production and maturation, and can in some cases be triggered by over-activity of white blood cells, some researchers speculate that there may be a connection between these disorders and NHL.
(J) Continuous antigenic stimulation
Many of the possible causes of NHL that we have discussed in the preceding paragraphs may act by soliciting an ongoing reaction from our immune system. Some researchers believe that chemicals, infections, or allergic or auto-immune reactions are all capable of producing an ongoing immune system reaction that triggers NHL and other related illnesses. This is sometimes called continuous antigenic stimulation.
The substance or infectious agent itself may not be causing the cancer, but the immune system reacting to the substance is. For example, some B-cell lymphomas such as gastric MALT lymphomas appear unable to grow unless white blood cells specific for killing Helicobacter pylori bacteria are also present. This growth of cancer only following action by part of the immune system also is seen in the failure of growth of grafted B-cell tumors in severe combined immunodeficiency (SCID) mice, which are bred without immune systems for research purposes. But when missing T-cells are injected, the tumors begin to grow.
Currently, the best place for this theory remains within the laboratory. It is of little practical import whether a substance, or the immune system's reaction to it, is to blame for cancer if simply avoiding a substance can reduce your risk.
The possibility for dangerous continuous antigenic stimulation is also the basis for the FDA ruling requiring warning labels on some nutritional supplements, such as melatonin, sold as immune boosters.
(K) The aging immune system
In opposition to continuous antigenic stimulation discussed above, some researchers feel that the greatly increased rate not only of NHL, but of most other cancers among those over age 65, hints at a general weakening of the immune system with age. Others feel that this more likely may be a product of the modern world we live in: that genetic damage from substances in an industrialized environment accumulates over time and first becomes apparent among the oldest.[14]
