Lymphomas (Non-Hodgkin's)

Description

Risk Factors

Non-Hodgkin's lymphoma (NHL) is now the fifth leading cause of cancer death in the United States. An estimated 53,400 Americans will have been diagnosed with non-Hodgkin's lymphomas in 2003. 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 due to 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 malignancy can develop in people at all ages, including children, although the peak onset is between ages 45 and 60. In general, the incidence of NHL is 50% higher in men than in women, and 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.

It should be noted that risks for NHL among men vs. women and among African Americans vs. Caucasians may vary by lymphoma subtype, according to a major 2000 study. 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

Risk in a sibling of a person with the disease is more than two times higher than in 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. People with small lymphocytic lymphomas tended to be thinner and people over 50 with B-CLL were more likely to be heavier, but, overall, the researchers did not find any important relationships with 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. (Interestingly, in one major study, milk, which, except for skim, contains animal fat, appeared to confer protection.)

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.

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:

• Epstein-Barr virus, the cause of mononucleosis, is highly associated with Burkitts disease and NHLs associated with immunodeficiency diseases. It is also a risk factor Hodgkin's disease
• 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.
• People who have gastritis (stomach inflammation) due to Helicobacter pylori or H. heilmannii bacterial infections) are at increased risk for mucosa-associated lymphoid tissue lymphomas (MALT). (In some patients who have this lymphoma in an early stage and have evidence of either infection, the use of antibiotics to eliminate the bacteria may result in complete remission of the lymphoma.)
• Human herpesvirus 8 has been associated with NHL.
• Borrelia burgdorferi, the spirochete (corkscrew-shaped bacterium) that causes Lyme disease, has been associated with primary B-cell lymphoma (which mostly occurs on legs and only infrequently spreads to areas outside the skin).

Click the icon to see an image of lyme disease.

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.

Note: 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.

• 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 AIDS patients. 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 US, but non-AIDS-related NHL continues to increase.
• Patients with a history of autoimmune diseases, including rheumatoid arthritis, Hashimoto's thyroiditis, Crohn's disease, and Sjgren's syndrome are at a slightly increased risk for certain NHLs, such as marginal zone lymphomas.
• 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.
• Patients who have had high-dose chemotherapy with stem-cell transplantation are at higher risk.
• 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. Of note, there appears to be no adverse association between NHL and allergy, which is an overactive response of the immune system and is the most common immune disorder. In fact, one study found a decreased risk for certain lymphomas in people with plant or pet allergies or a history of bee or wasp stings.

Industrial Chemicals and Other Environmental Risk Factors

Overexposure to a number of industrial and agricultural chemicals have been frequently linked to an increased risk for lymphomas. The data, however, is not consistent. Studies suggesting a higher risk include the following:

• Dioxin is a possible suspect as a chemical risk factor for NHL. A 2000 study, for example, found an increased incidence in people who worked around solid waste incinerators and were exposed to dioxin. And, a population study in Italy reported the highest risk with exposure to dioxin after 15 years.
• A number of studies have found an association between NHL and certain pesticides and herbicides, although more research is needed to confirm any risk.
• 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. (In this study, farmers also had a lower risk than others.)
• In a 2001 study, typesetters had a higher risk for NHL, which warrants further research.
• 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 or Factors Associated with Non-Hodgkins Lymphomas

Factors During and After Pregnancy. 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 six months, on the other hand, may offer some protection.)