| |
Non-Hodgkin's
Lymphoma
Sheila Zahm, Ph.D.*
Lymphomas are cancers that affect the
white blood cells of the immune system. They are characterized by the abnormal
growth of lymphocytes, the infection-fighting cells in the lymph nodes, spleen,
and thymus. The tonsils, stomach, small intestine, and skin may also be
affected. Primary lymphomas of the skin such as mycosis fungoides and Sezary's
disease are extremely rare. Burkitt's lymphoma, rare in most of the world, is
the most common childhood cancer in Central Africa, and is one of the most
aggressive of all human cancers.
Lymphomas are usually classified as
Hodgkin's disease or non-Hodgkin's lymphoma. An estimated 45,000 new cases of
non-Hodgkin's lymphoma were diagnosed in the United States in 1994 (Boring et
al., 1994). Incidence per 100,000 is 18.6 among white males, 12.0 among white
females, 12.8 among black males, and 8.1 among black females. In the United
States, five-year survival is 53 percent for white patients and 45 percent for
black patients. The highest incidence rates internationally for non-Hodgkin's
lymphoma were observed for the United States and Canada (Parkin et al., 1992),
although comparing incidence, survival, and mortality statistics among countries
may be difficult because of differing classification systems used for these
diseases.
Between 1973 and 1991, the 73 percent
increase in the incidence of non-Hodgkin's lymphoma was one of the largest among
the major cancer sites in the United States (Ries et al., 1994). Part of the
increase in incidence of non-Hodgkin's lymphoma in recent years has been related
to AIDS. Non-Hodgkin's lymphoma is about 60 times more common in AIDS patients
than in the general U.S. population (Beral et al., 1991). Gail et al. (1991)
estimated that between 8 and 27 percent of all non-Hodgkin's lymphoma cases that
occurred in the United States in 1992 were a direct consequence of infection
with human immunodeficiency virus (HIV). AIDS, however, cannot explain the
increase in non-Hodgkin's lymphoma observed over a period that began years
before the AIDS epidemic surfaced, and continues to be observed in the absence
of HIV infection.
Other immunodeficiency states, both
genetic and induced by medications or illness, are also associated with
extremely high risks of non-Hodgkin's lymphoma (Filipovich et al., 1992; Kinlen,
1992). Kidney transplant patients, whose immune systems are suppressed with
medications, develop non-Hodgkin's lymphomas 40 to 100 times more frequently
than expected (Fraumeni and Hoover, 1977; Kinlen et al., 1979). As an
alternative mechanism, immunostimulation may play a role in the high risks
observed in some groups with immune abnormalities (Hoover, 1992).
Viruses other than HIV have also been
linked to non-Hodgkin's lymphoma (Mueller et al., 1992). Human T-lymphotropic
virus, type I (HTLV-I) has been linked to certain types of adult T-cell
leukemias and lymphomas found mostly in southern Japan, parts of the Caribbean
and Africa, and the southeastern United States (Mueller, 1991), but is not a
likely factor in the widespread increase in non-Hodgkin's lymphoma. On the other
hand, Epstein-Barr virus (EBV) is ubiquitous--by adulthood almost everyone has
been exposed to it and has developed antibodies against it. EBV has been linked
to Burkitt's lymphoma in African children (Ziegler, 1981) and is linked to
non-Hodgkin's lymphoma in persons with acquired or genetic immunosuppression
(Mueller et al., 1992). Its role in non-Hodgkin's lymphoma in the general
population is under investigation.
Pesticides have been associated with
non-Hodgkin's lymphoma in studies of farmers, other pesticide applicators,
manufacturing workers and other exposed populations (Zahm and Blair, 1992). One
study, conducted in Kansas, revealed a striking association between
non-Hodgkin's lymphoma and the use of herbicides, particularly 2,4-D (Hoar et
al., 1986). The risk of non-Hodgkin's lymphoma rose with increasing frequency of
use of herbicides, rising almost eight-fold among 2,4-D-using farmers who
handled herbicides 20 or more days per year. Another study conducted in Nebraska
also found a significantly increasing risk of non-Hodgkin's lymphoma with
increasing use of 2,4-D, although the risks were lower than observed in Kansas (Zahm
et al., 1990). Associations between non-Hodgkin's lymphoma and herbicides were
also found in Sweden (Hardell et al., 1981) and Canada (Wigle et al., 1990) and
with chlorophenols in Sweden (Hardell et al., 1979). Canine malignant lymphoma
has also been associated with dog owner use of 2,4-D and commercial pesticide
lawn treatments (Hayes et al., 1991). Grain handlers exposed to pesticides,
grain dusts, and organic solvents have been found to have a five-fold risk of
nonHodgkin's lymphoma (Alavanja et al., 1990). Exposure to organophosphate
insecticides may also play a role in the development of non-Hodgkin's lymphoma (Zahm
et al., 1990; Cantor et al., 1992). Risks to the general population, who are
exposed at much lower levels than occupationally exposed groups, have not been
well studied.
Occupations other than agriculture that
have been associated with nonHodgkin's lymphoma include rubber workers (Monson
and Nakano, 1976; Wilcosky et al., 1984), petroleum refining workers (Delzell et
al., 1988), vinyl chloride workers (Chiazze et al., 1977), chemists (Li et al.,
1969; Searle, 1978; Olin and Ahlbom, 1980), dry cleaners (Blair et al., 1990),
and aircraft maintenance workers (Spirtas et al., 1991). The etiologic agents
responsible for these excesses have not been identified definitively, but the
occupations have in common exposure to organic solvents.
Hair dye use, particularly long-term use
of dark-color products, and occupational exposure to hair coloring products were
associated with lymphatic and hematopoietic malignancies, including
non-Hodgkin's lymphoma, in several recent studies (Cantor et al., 1988; Zahm et
al., 1992; Thun et al., 1994; Linos et al., 1994; Giles et al., 1984).
Hair-coloring products contain compounds that are mutagenic, carcinogenic, and
teratogenic in animals. While there was no or little increased risk reported for
overall use of hair coloring products, long-term dark-product users experienced
two- to four-fold increased risk in some studies. The role of hair coloring
products in the etiology of these malignancies, however, remains controversial (Zahm
et al., 1994; Colditz 1994; Thun et al., 1994). The studies that reported the
excesses were not conducted to investigate hair-coloring products as their
primary focus, and so the questionnaires lack detail that is critical to judging
causality. It is important to resolve the questions about the possible
carcinogenicity of hair-coloring products. Approximately 35 to 60 percent of
women and 10 percent of men use hair-coloring products (Zahm et al., 1994; Zahm
et al., 1992), and use appears to be rising in young people (Sturgeon and Hartge,
submitted).
In summary, the incidence of non-Hodgkin's
lymphoma has been rising inexplicably. A continued, perhaps even larger,
increase is anticipated because of AIDS-related cases. The cofactors that
predispose AIDS cases to lymphoma need elucidation and research is needed into
other possible causes of non-Hodgkin's lymphoma, such as hair-coloring products,
pesticides, nitrates, solvents, other industrial chemicals, and viruses other
than HIV.
REFERENCES
Alavanja MC, Blair A and Masters MN:
Cancer mortality in the U.S. flour industry. J Natl Cancer Inst 82:840-848,
1990.
Beral V, Peterman T, Berkelman R, et al.:
AIDS-associated non-Hodgkin lymphoma. Lancet 337:805-809, 1991.
Blair A, Stewart PA, Tolbert P, et al.:
Cancer and other causes of death among a cohort of dry cleaners. Br J Ind Med
47:162-168, 1990.
Boring CC, Squires TS, Tong T, et al.:
Cancer Statistics 1994. CA Cancer J Clin 44:7-26, 1994.
Cantor KP, Blair A, Everett G, et al.:
Pesticides and other agricultural risk factors for non-Hodgkin's lymphoma among
men in Iowa and Minnesota. Cancer Res 52:2447-2455, 1992.
Cantor KP, Blair A, Everett G, et al.:
Hair dye use and risk of leukemia and lymphoma. Am J Public Health 78:570-571,
1988.
Chiazze L Jr, Nichols WE and Wong O:
Mortality among employees of PVC fabricators. J Occup Med 19:623-628, 1977.
Colditz GA: Response to "Hair
coloring products: Safe or still suspect?" J Natl Cancer Inst 86:943, 1994.
Delzell E, Austin H and Cole P:
Epidemiologic studies of the petroleum industry. Occup Med, State of the Art
Reviews 3:455-474, 1988.
Filipovich AH, Mathur A, Kamat D, et al.:
Primary immunodeficiencies: Genetic risk factors for lymphoma. Cancer Res 52 (suppl):5465s-5467s,
1992.
Fraumeni JF Jr and Hoover R:
Immunosurveillance and cancer: Epidemiologic observations. J Natl Cancer Inst
Monogr 47:121-126, 1977.
Gail MH, Pluda JM, Rabkin CS, et al.:
Projections of the incidence of non-Hodgkin's lymphoma related to acquired
immunodefiency syndrome. J Natl Cancer Inst 83:695-701, 1991.
Giles GG, Lickiss JN, Baikie MJ, et al.:
Myeloproliferative and lymphoproliferative disorders in Tasmania, 1972-80:
Occupational and familial aspects. J Natl Cancer Inst 72:1233-1240, 1984.
Hardell L and Sandstrom A: Case-control
study: Soft-tissue sarcoma and exposure to phenoxyacetic acids or chlorophenols.
Br J Cancer 39:711-171, 1979.
Hardell L, Eriksson M, Lenner P, et al.:
Malignant lymphoma and exposure to chemicals, especially organic solvents,
chlorophenols and phenoxy acids: A case-control study. Br J Cancer 43:169-176,
1981.
Hayes HM, Tarone RE, Cantor KP, et al.:
Case-control study of canine malignant lymphoma: Positive association with dog
owner's use of 2,4-dichlorophenoxyacetic acid herbicides. J Natl Cancer Inst
83:1226-1231, 1991.
Hoar SK, Blair A, Holmes FF, et al.:
Agricultural herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA
256:1141-1147, 1986.
Hoover RN: Lymphoma risks in populations
with altered immunity--a search for mechanism. Cancer Res 52 (suppl):5477s-5478s,
1992.
Kinlen L: Immunosuppressive therapy and
acquired immunological disorders. Cancer Res 52 (suppl): 5474s-5476s, 1992.
Kinlen LJ, Shiel AGR, Peto J, et al:
Collaborative United Kingdom-Australasian study of cancer in patients treated
with immunosuppressive drugs. BMJ 2:1461-1466, 1979.
Li FP, Fraumeni JF Jr, Mantel N, et al.:
Cancer mortality among chemists. J Natl Cancer Inst 43:1159-1164, 1969.
Linos A, Kiamouris C, Foukanelis T, et
al.: A case-control study of non-Hodgkin's lymphoma (abstract). Am J Epidemiol
139:S46, 1994.
Monson RR and Nakano KK: Mortality among
rubber workers. I. White male union employees in Akron, Ohio. Am J Epidemiol
103:284-296, 1976.
Mueller N: The epidemiology of HTLV-I
infection. Cancer Causes and Control 2:37-52, 1991.
Mueller NE, Mohar A and Evans A: Viruses
other than HIV and non-Hodgkin's lymphoma. Cancer Res 52 (suppl):5479s-5481s,
1992.
Olin GR and Ahlbom A: The cancer mortality
among Swedish chemists graduated during three decades. A comparison with the
general population and with a cohort of architects. Environ Res 22:154-161,
1980.
Parkin DM, Muir CS, Whelan S, et al.:
Cancer Incidence in Five Continents, vol VI. IARC Scientific Publication No.
120. World Health Organization, International Agency for Research on Cancer,
Lyon, 1992.
Ries LAG, Miller BA, Hankey BF, et al.:
SEER Cancer Statistics Review, 1973-1991: Tables and Graphs, National Cancer
Institute. NIH Publ. No. 94-2789, Bethesda, MD, 1994.
Searle CE, Waterhouse JAH, Herman BA, et
al.: Epidemiological study of the mortality of British chemists. Br J Cancer
38:192-193, 1978.
Spirtas R, Stewart PA, Lee JS, et al.:
Retrospective cohort mortality study of workers at an aircraft maintenance
facility. I. Epidemiological results. Br J Ind Med 48:515-530, 1991.
Sturgeon SR and Hartge P: Trends in the
use of hair coloring products among American men and women (submitted).
Thun MJ, Altekruse SF, Namboodiri MM, et
al.: Hair dye use and risk of fatal cancers in U.S. women. J Natl Cancer Inst
86:210-215, 1994.
Thun MJ, Calle EE, Myers DG, et al.:
Response to "Hair coloring products: Safe or still suspect?" J Natl
Cancer Inst 86:943-944, 1994.
Wigle DT, Semenciw RM, Wilkins K, et al.:
Mortality study of Canadian male farm operators: Non-Hodgkin's lymphoma
mortality and agricultural practices in Saskatchewan. J Natl Cancer Inst
82:575-582, 1990.
Wilcosky TC, Checkoway H, Marshall EG, et
l.: Cancer mortality and solvent exposures in the rubber industry. Am Ind Hyg
Assoc J 45:809-811, 1984.
Zahm SH and Blair A: Pesticides and
non-Hodgkin's lymphoma. Cancer Res 52 (suppl) :5485s-5488s, 1992.
Zahm SH, Blair A and Fraumeni JF, Jr: Hair
coloring products: Safe or still suspect? J Natl Cancer Inst 86:941-943, 1994.
Zahm SH, Wiesenburger DD, Babbitt PA, et
al.: A case-control study of non-Hodgkin's lymphoma and the herbicide
2,4-dichlorophenoxyacetic acid (2,4-D) in eastern Nebraska. Epidemiology
1:349-356, 1990.
Zahm SH, Weisenburger DD, Babbit PA, et
al.: Us of hair coloring products and the risk of lymphoma, multiple myeloma,
and chronic lymphocytic leukemia. Am J Public Health 82:990-998, 1992.
Ziegler JL: Burkitt's lymphoma. N Engl J
Med 305:735-745, 1981.
*
From the Environmental Epidemiology Branch, Division of Cancer Etiology,
National Cancer Institute, Bethesda, Maryland
National Cancer Institute
Path:
Home>Education>Health
Information>Non-Hodgkin's
Lymphoma
|
|
