Non-Hodgkin's lymphoma
Description
An in-depth report on the causes, diagnosis, and treatment of non-Hodgkin's lymphoma.
Alternative Names
Lymphoma - non-Hodgkin's; NHL; B-cell lymphomas
Risk Factors
An estimated 58,870 Americans were diagnosed with non-Hodgkin's lymphomas in 2006 and about 18,840 people died of the disease. For the past 25 years, the incidence in NHL has increased continuously. Most of this increase has been observed in people over 65. There is some evidence that the rates are now stabilizing or even declining.
Part of the reason for the dramatic rise is AIDS, which increases the risk for high-grade lymphomas. However, even after eliminating changes in diagnosing NHLs and known causes such as AIDS, there remains a 40% higher incidence over the past 40 years. The number of cases in which lymphomas first occur outside the lymph nodes has also increased compared to those limited to the nodes. (This observed increase, however, may in large part be due to different methods of diagnosing lymphomas).
Gender, Age, and Ethnicity
The cancer can develop in people at all ages, including children, although it is most common in those between the ages of 45 - 60. In general, the incidence of NHL is 50% higher in men than in women. This higher rate has been observed in many countries. Nevertheless, recent reports suggest that the rate is leveling off or even declining in men, but is increasing in women, particularly African-American women. Overall, the risk is slightly higher in Caucasians than in African-Americans.
A major 2000 study found that the risks for NHL among men versus women and among African-Americans versus Caucasians may vary by lymphoma subtype. For example, follicular lymphomas were significantly higher in Caucasians than in African Americans and there was little gender difference. High-grade lymphomas were the most rapidly increasing type, particularly among men, with follicular lymphomas increasing most rapidly in African-American men.
Other studies have also reported ethnic differences by specific lymphoma subtypes. For example, follicular lymphomas constitute 20% of all NHLs in Western nations but are very uncommon in Asia and in developing countries.
Family History
The brother or sister of a person with the disease has more than twice the risk of developing NHL than the general population. Some cases of NHL in such cases are due to inherited disorders of the immune system. Studies suggest, however, that such family clusters are more likely to be due to environmental conditions that trigger the genetic factors.
Lifestyle Factors
Because of the rapid rise in NHL, investigators are looking for lifestyle factor that may contribute to this increase.
Body Weight, Shape, and Exercise.
A 2002 study looked for any associations between lymphomas and body weight or shape or amounts of exercise. Overall, the researchers did not find any important relationships between non-Hodgkin's lymphomas and these lifestyle factors.
Dietary Factors.
A number of studies have observed an association between an increased risk for non-Hodgkin's lymphomas and high consumption of red meat (beef, pork, and lamb). Some have also found a higher risk with animal fats and trans fatty acids (hydrogenated polyunsaturated fats, which are contained in hard margarines and commercial baked goods and fast foods). There appears to be no higher risk with natural polyunsaturated fats (found in most vegetable and fish oils), and in fact, fish may be protective. Some evidence suggests that milk may also be protective.
One major study observed a reduction in risk with high intake of vegetables. Another found no protection from vegetables, but did with diets rich in fruit. Vitamin supplements have no effect on NHL.
Despite these kinds of reports, the influence of diet on the development of non-Hodgkin's lymphomas remains speculative.
Alcohol Use.
Studies on alcohol have been mixed, with some showing a higher risk, some a lower risk, and some no difference at all. A 2002 study reported, for example, some reduced risk from wine drinking but not from beer or other spirits. A 2005 study found that alcoholic beverages were linked to a reduced risk of developing NHL, but that the amount of protection depended on the type of NHL.
Smoking.
There is no evidence that smoking increases the risk for NHL itself, although it has been linked with high-grade and follicular NHLs in people with lymphomas.
Infections
Viruses or other microorganisms also play a role in some lymphomas. A number are being investigated:
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Epstein-Barr virus, the cause of mononucleosis, is highly associated with Burkitt's disease and NHLs associated with immunodeficiency diseases. It is also a risk factor for Hodgkin's disease
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Adult T-cell leukemia-lymphoma, which appears to be caused by a virus known as HTLV-I, has been found in southwestern Japan, the Caribbean, and the southeastern United States.
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People who have stomach inflammation due to
Helicobacter pylori
or
H. heilmannii
bacteria are at increased risk for mucosa-associated lymphoid tissue lymphomas (MALT). (The use of antibiotics to get rid of the bacteria may cause remission in some patients who have an early stage form of lymphoma in an early stage.)
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Human herpesvirus 8 has been associated with NHL.
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Borrelia burgdorferi
, the bacteria that causes Lyme disease, has been associated with primary B-cell lymphoma.
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Heavy antibiotic use during adulthood may increase risk. A 2005 study found that adults who used antibiotics more than 10 times had 1.8 times the risk of developing NHL than nonusers. However, researchers were not certain if antibiotics themselves, or the underlying infections they treated, were responsible for the increased risk.
Studies are reporting a higher prevalence of viral hepatitis C and B in patients with lymphomas, although such viruses do not appear to play a major role in triggering lymphoma.
One study reported a
lower
risk for certain lymphomas in people with a history of receiving five or more different vaccines.
Disorders of the Immune System
Patients with diseases or conditions that affect the immune system may be at higher risk for lymphomas:
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HIV-positive patients and those with full-blown AIDS are at higher risk for NHL, and the disease is more likely to be widespread in these patients than in those without the immune disease. Most AIDS-related NHLs are high-grade lymphomas. Burkitt's lymphoma is often seen in patients with AIDS. Although these patients have had a very poor prognosis, advances in antiviral therapy for HIV now allow better management of NHL with some success in achieving favorable outcomes. Part of the dramatic increase in NHL incidence over the past decades can, in fact, be traced to AIDS. However, one 2002 study observed that AIDS is now declining in the U.S., but non-AIDS-related NHL continues to increase.
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Patients with a history of autoimmune diseases, including rheumatoid arthritis (RA), Hashimoto's thyroiditis, Crohn's disease, and Sjögren syndrome are at an increased risk for certain NHLs, such as marginal zone lymphomas. [See section:
Other Conditions Associated with Non-Hodgkin's Lymphomas
.]
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People who have organ transplants are at higher risk for NHL, probably due to multiple factors, including the drugs used to suppress the immune system and the transplanted organ itself.
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Patients who have had high-dose chemotherapy with stem-cell transplantation are at higher risk.
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Other immunodeficiency syndromes that put people at risk for NHL include Chediak-Higashi syndrome, ataxia-telangiectasia, B-cell lymphoproliferative syndrome, Bruton agammaglobulinemia, common variable immunodeficiency, and Wiskott-Aldrich syndrome.
Note on Allergies: There appears to be no association between NHL and allergy, which is an overactive response of the immune system and is the most common immune disorder.
Industrial Chemicals and Other Environmental Risk Factors
Overexposure to a number of industrial and agricultural chemicals has been frequently linked to an increased risk for lymphomas. The data, however, are not consistent.
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Organochlorines are chemicals produced when solid waste is burned. These by-product chemicals include dioxin, polychlorinated biphenyls (PCBs), and furans. Many studies have indicated that exposure to these chemicals increases the risk of developing NHL.
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A number of studies have found an association between NHL and certain pesticides and herbicides, although more research is needed to confirm any definitive risk.
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White spirits, thinners, phenoxy herbicides, wood preservative, aviation gasoline, plastic, and rubber chemicals have been associated with a higher risk for lymphomas. Specifically, in one study, painters and lumberjacks had a higher risk for NHL, while office and house workers had a lower risk.
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Some studies have found an association with long duration and early use of permanent dark hair dyes. There is no consistent evidence, however, that hair dye increases the risk for lymphomas.
Other Conditions Associated with Non-Hodgkin's Lymphomas
Autoimmune Diseases.
Patients with autoimmune diseases may have increased risks for developing NHL. A 2005 review found that patients with Sjögren syndrome had 18.8 times more risk for NHL than healthy patients. Systemic lupus erythematosus increased risk by 7.4 times, and rheumatoid arthritis increased risk by 3.9 times. For patients with rheumatoid arthritis, the lymphoma risk appears highest for those with very severe and chronic forms of this autoimmune disease.
Tumor necrosis factor (TNF) blockers used to treat autoimmune conditions -- such as infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira) -- may also increase the risk for developing NHL. According to one study, lymphoma rates for patients who took infliximab for Crohn's disease or RA were six times higher than those found in the general public. However, several 2006 studies suggested that the inflammatory process of rheumatoid arthritis, rather than its drug treatments, is the main factor in increasing lymphoma risk.
Pregnancy and Childbirth.
One study observed a higher risk for lymphomas in children with a low weight at birth or with mothers who were heavy smokers during pregnancy. (Breastfeeding for more than 6 months, on the other hand, may offer some protection.)
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Review Date: 1/17/2007
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Reviewed By: Harvey Simon, MD, Editor-in-Chief, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.
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