Cancer Research UK : Non-Hodgkin Lymphoma risk factors

Non-Hodgkin Lymphoma risk factors

This page presents information on non-Hodgkin lymphoma (NHL) risk factors including infectious agents, immunosuppression, genetic susceptibility and environmental factors.

There are a number of well-established risk factors for the development of NHL, although the majority of cases have no clearly identifiable cause. A number of reviews have concluded that the large increases in incidence could not be wholly explained by known risk factors.1-3

NHL risk factors - infectious agents

Various microbial agents have been associated with NHL, although infection is only one step in the complex chain of events required for cancer development and NHL is not in any sense an infectious disease.

Some of the worldwide increase in NHL is associated with immunodeficiency 4, increasingly common with the HIV infection epidemic. However, the rising incidence of NHL in many countries predates the HIV epidemic. The increased risk of NHL in patients with HIV is well documented, although only approximately 3-5% of people with HIV and AIDS will develop NHL.5-7

The relative risks of NHL in people with AIDS ranges between 15 for low-grade and T-cell NHL and 400 for high-grade NHL.8,9

Infection with Epstein-Barr virus (EBV) is associated with both Burkitt lymphoma, prevalent in malarial areas of sub-Saharan Africa but rare in developed countries, and ‘post-transplant’ lymphoma.10

There is growing evidence for a causal link between infections and lymphomas of mucosa-associated lymphoid tissue (MALT) such as Helicobacter pylori and primary gastric lymphoma.11 and Chlamydia psittaci with orbital lymphoma 12.

NHL risk factors - immunosuppression

The use of immunosuppression with organ transplantation is associated with an increased risk of non-Hodgkin lymphoma and in a proportion of cases EBV is implicated 13. The risk of lymphoma rises with the duration and depth of immunosuppression. Around 13% of heart, and 33% of heart/lung recipients have been reported to develop NHL in one series. 14,15

The chronic immunosuppression associated with rheumatoid arthritis and its treatment also carries a slightly increased risk of lymphoma.16

NHL risk factors - genetic susceptibility

The role of genetic susceptibility is poorly defined at present. A high incidence of B cell lymphomas has been associated with ataxia telangiectasia and with genetically determined immune deficiency states such as common variable hypogammaglobulinaemia.17 Familial clusters of NHL are also known to occur, although the relative contribution of genetic and environmental factors is undefined. Coeliac disease is a known predisposing factor to intestinal T cell lymphoma.

NHL risk factors - environmental factors

Occupational exposure to chemicals, particularly agricultural chemicals, has been suggested by several studies as a risk factor for NHL.18-20 Immunosuppression can also be caused by agricultural and industrial chemicals, and these could be responsible for at least some of the rise in incidence of NHL.

There are local excesses of NHL in rural areas, relatively high incidence rates among farmers and horticulturalists21, and associations between exposure to agricultural biocides and risk of NHL.

However, whilst atrazine, lindane and phenoxy herbicides such as 2,4D have all been implicated in some studies, current evidence does not show a clear-cut association between any specific agricultural chemical and lymphoma.22-25

Associations have also been found between exposure to tetrachloroethylene, a solvent widely used for dry cleaning and degreasing, and various forms of cancer including non-Hodgkin lymphoma. Although the published evidence for increased risk of NHL among people working with tetrachloroethylene is limited to three cohort studies, their results are consistent.26,27

References for non-Hodgkin lymphoma risk factors

Hartge P, Devesa SS. Quantification of the impact of known risk factors on time trends in non-Hodgkin's lymphoma incidence. Cancer Res 1992;52(19 Suppl):5566s-9s
Obrams GI, O'Conor G. The emerging epidemic of non-Hodgkin's lymphoma: current knowledge regarding etiological factors. Time trends and pathological classification: a summary. Cancer Res 1992;52(19 Suppl):5570s.
Swerdlow AJ. Epidemiology of Hodgkin's disease and non-Hodgkin's lymphoma. Eur J Nucl Med Mol Imaging 2003;30 Suppl 1:S3-12.
Filipovich AH, Mathur A, Kamat D, Shapiro RS. Primary immunodeficiencies: genetic risk factors for lymphoma. Cancer Res 1992;52(19 Suppl):5465s-7s.
Serraino D, Salamina G, Franceschi S, et al. The epidemiology of AIDS-associated non-Hodgkin's lymphoma in the World Health Organization European Region. Br J Cancer 1992;66(5):912-6.
Pallesen, G., S.J. Hamilton-Dutoit, and X. Zhou, The association of Epstein-Barr virus (EBV) with T cell lymphoproliferations and Hodgkin's disease: two new developments in the EBV field. Adv Cancer Res, 1993. 62: p. 179-239.
Franceschi S, Dal Maso L, La Vecchia C. Advances in the epidemiology of HIV-associated non-Hodgkin's lymphoma and other lymphoid neoplasms. Int J Cancer 1999;83(4):481-5.
Tulpule A, Levine A. AIDS-related lymphoma. Blood Rev 1999;13(3):147-50.
Dal Maso L, Rezza G, Zambon P, et al. Non-Hodgkin lymphoma among young adults with and without AIDS in Italy. Int J Cancer 2001;93(3):430-5.
Epstein MA, Achong BG, Barr YM. Virus Particles In Cultured Lymphoblasts From Burkitt's Lymphoma. Lancet 1964;15:702-3.
Wotherspoon AC, Ortiz-Hidalgo C, Falzon MR, Isaacson PG. Helicobacter pylori-associated gastritis and primary B-cell gastric lymphoma. Lancet 1991;338(8776):1175-6.
Ferreri AJ, Guidoboni M, Ponzoni M, et al. Evidence for an association between Chlamydia psittaci and ocular adnexal lymphomas. J Natl Cancer Inst 2004;96(8):586-94.
Kawashima K, Hayashi K, Ohnoshi T, Teramoto N, Kimura I. Epstein-Barr virus-associated post-transplant non-Hodgkin's lymphoma: establishment and characterization of a new cell line. Jpn J Cancer Res 1994;85(11):1080-6.
Opelz G, Henderson R. Incidence of non-Hodgkin lymphoma in kidney and heart transplant recipients. Lancet 1993;342(8886-8887):1514-6.
Swinnen LJ, Costanzo-Nordin MR, Fisher SG, et al. Increased incidence of lymphoproliferative disorder after immunosuppression with the monoclonal antibody OKT3 in cardiac-transplant recipients. N Engl J Med 1990;323(25):1723-8.
Kamel OW, van de Rijn M, Hanasono MM, Warnke RA. Immunosuppression-associated lymphoproliferative disorders in rheumatic patients. Leuk Lymphoma 1995;16(5-6):363-8.
Kersey JH, Shapiro RS, Filipovich AH. Relationship of immunodeficiency to lymphoid malignancy. Pediatr Infect Dis J 1988;7(5 Suppl):S10-2.
Rusiecki JA, De Roos A, Lee WJ, et al. Cancer incidence among pesticide applicators exposed to atrazine in the Agricultural Health Study. J Natl Cancer Inst 2004;96(18):1375-82.
Raaschou-Nielsen O, Hansen J, McLaughlin JK, et al. Cancer risk among workers at Danish companies using trichloroethylene: a cohort study. Am J Epidemiol 2003;158(12):1182-92.
Buckley JD, Meadows AT, Kadin ME, Le Beau MM, Siegel S, Robison LL. Pesticide exposures in children with non-Hodgkin lymphoma. Cancer 2000;89(11):2315-21.
Simpson J, Roman E, Law G, Pannett B. Women's occupation and cancer: preliminary analysis of cancer registrations in England and Wales, 1971-1990. Am J Ind Med 1999;36(1):172-85.
Fleming LE, Bean JA, Rudolph M, Hamilton K. Mortality in a cohort of licensed pesticide applicators in Florida. Occup Environ Med 1999;56(1):14-21.
Buckley JD, Meadows AT, Kadin ME, Le Beau MM, Siegel S, Robison LL. Pesticide exposures in children with non-Hodgkin lymphoma. Cancer 2000;89(11):2315-21.
Dich J, Zahm SH, Hanberg A, Adami HO. Pesticides and cancer. Cancer Causes Control 1997;8(3):420-43.
Wiklund K, Dich J. Cancer risks among male farmers in Sweden. Eur J Cancer Prev 1995;4(1):81-90.
Wartenberg D, Reyner D, Scott CS. Trichloroethylene and cancer: epidemiologic evidence. Environ Health Perspect 2000;108 Suppl 2:161-76.
IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Dry cleaning, Some Chlorinated Solvents and Other Industrial Chemicals. Lyon: IARC; 1995.

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