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

Infections are the most well-characterised cause of NHL. A study published in December 2011 estimated that, in 2010, more than 4% of NHL cases in the UK were linked to infections.8

Non-Hodgkin lymphoma 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.5-7 The risk of NHL overall in people with HIV or AIDS, according to the latest meta-analysis, is increased almost 80-fold compared to the background rate. 28 However, many of the studies included in this analysis were carried out prior to the introduction of highly active anti-retroviral therapy (HAART) and most of the patients surveyed already had AIDS, onset of which is delayed with HAART. Cohort studies carried out in the US suggest that, following the introduction of HAART, the relative risk of NHL in people with HIV is about 6.5.8

A study published in December 2011 estimated that less than 1% of NHL cases in the UK in 2010 were linked to infection with HIV.8

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 EBV is present in two-thirds of AIDS-related lymphomas.29 It has been estimated that less than 1% of NHL cases in the UK are linked to infection with EBV. This estimate excludes EBV-related cases where there was co-infection with HIV, as these cases were included in the HIV-related estimate given above.8

There is a strong association between Helicobacter pylori and lymphomas of mucosa-associated lymphoid tissue (MALT) in the stomach. 11 A study published in December 2011 estimated that around 3% of NHL cases in the UK in 2010 were linked to infection with H.pylori. 8 Hepatitis C virus infection increases risk of NHL. The most recent meta-analysis of published studies showed a 2.5-fold risk increase in the summary risk ratio from case-control studies and a 2-fold risk increase based on findings from three cohort studies.12 The UK study mentioned above estimated that less than 1% of NHL cases in the UK are linked to Hepatitis C infection.8 Infection with Human T-Lymphotropic Virus 1 causes a small number of cases of NHL in developed countries (estimated as 0.2% of NHL cases in the UK in 2010).8

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Immunosuppression 

The use of immunosuppression with organ transplantation is associated with an increased risk of NHL 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 latest meta-analysis showed an 8-fold increased risk of NHL in transplant recipients.28

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Autoimmune conditions

The chronic immune stimulation associated with the autoimmune conditions, haemolytic anaemia, systemic lupus erythematosus and Sjogren syndrome also carries an increased risk of lymphoma. 16 Coeliac disease is associated with an increased risk of T-cell lymphoma specifically.16 However, in the case of this condition, improved management has been linked with a reduction in the risk in the last three-four decades.30 An increased risk of NHL has also been shown for people with a sibling with coeliac disease.30

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Genetic susceptibility

A family history of NHL has been linked to almost a doubling of risk in siblings and offspring of cases, with higher risks for concordant tumour subtypes. 17. 

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Environmental factors

Occupational exposure to chemicals, particularly agricultural chemicals, has been suggested by several studies as a risk factor for NHL. 18-25, 31 A meta-analysis of case-control studies reported a 35% increase in risk for people with occupational exposure to pesticides, increasing to 65% for more than 10 years' exposure.32

Occupational exposure to benzene has been linked to a 22% increase in NHL risk in a meta-analysis.33 Individual case-control studies have also shown an increased risk with occupational exposure to other aromatic hydrocarbon solvents and chlorinated hydrocarbon solvents.26,27, 34 However, an earlier meta-analysis found insufficient evidence of an increased risk with occupational exposure to trichloroethylene.35

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Body mass index (BMI)

Recent cohort studies have shown an increased risk of NHL for increasing body mass index (BMI).36,40 In addition, a meta-analysis showed a 40% increased risk of diffuse large B-cell NHL for people with a BMI of 30 or higher.37

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Diet and supplements

A reduction of NHL risk has been shown in the Iowa Women's Health cohort study for women with a higher intake of fruits and vegetables (31% risk reduction for highest versus lowest quartile of intake).38 However, an earlier cohort study did not show a reduction in risk.39

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References for non-Hodgkin lymphoma risk factors

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  23.   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.
  24.   Dich J, Zahm SH, Hanberg A, Adami HO. Pesticides and cancer. Cancer Causes Control 1997;8(3):420-43.
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  27.   Wang, R. et al., Occupational exposure to solvents and risk of non-Hodgkin lymphoma in Connecticut women. Am J Epidemiol 2009: 169(2):176-85.
  28.   Grulich A.E., et al., Incidence of cancers in people with HIV/AIDS compared with immunosuppressed transplant recipients: a meta-analysis. Lancet 2007;370(9581):59-67.
  29.   Parkin, D.M., The global health burden of infection-associated cancers in the year 2002. Int J Cancer 2006;118(12):3030-44.
  30.   Gao, Y., et al., Increased risk for non-Hodgkin lymphoma in individuals with celiac disease and a potential familial association. Gastroenterology 2009;136(1):91-8.
  31.   Bonner, M.R., et al., Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study. Cancer Causes Control 2010.
  32.   Merhi, M., et al., Occupational exposure to pesticides and risk of hematopoietic cancers: meta-analysis of case-control studies. Cancer Causes Control 2007;18(10):1209-26.
  33.   Steinmaus, C., et al., Meta-analysis of benzene exposure and non-Hodgkin lymphoma: biases could mask an important association. Occup Environ Med 2008;65(6):371-8.
  34.   Miligi, L., et al., Occupational exposure to solvents and the risk of lymphomas.Epidemiology 2006;17(5):552-61.
  35.   Mandel, J.H., et al., Occupational trichloroethylene exposure and non-Hodgkin's lymphoma: a meta-analysis and review. Occup Environ Med 2006;63(9):597-607.
  36.   Troy, J.D., et al., Associations Between Anthropometry, Cigarette Smoking, Alcohol Consumption, and Non-Hodgkin Lymphoma in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Am J Epidemiol 2010.
  37.  Larsson, S. C., and Wolk, A., Obesity and risk of non-Hodgkin's lymphoma: a meta-analysis. Int J Cancer 2007;121(7):1564-70.
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  39.  Thompson, C. A., et al., Intakes of fruits, vegetables, and related nutrients and the risk of non-Hodgkin's lymphoma among women. Cancer Epidemiol Biomarkers Prev 2000;9(5):477-85.
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