Risk Factors of Non Hodgkin Lymphoma


Due to the poorly understood aetiology of Non-lymphoma, Hodgkin’s identifying risk factors for NHL is difficult (NHL). However, research has shown that certain clinical and environmental factors, as well as genetic factors, are linked to an increased risk of NHL.


Non-Hodgkin’s lymphoma (NHL) includes all lymphomas except Hodgkin’s lymphoma. There have been frequent reports of an increase in the incidence of NHL worldwide over the last 30 years​1​. The etiology of NHL is a poorly understood and complicating the process of identifying NHL risk factors.

Some of the known risk factors for the development of NHL are as follows.

Clinical and environmental risk factors

Studies have reported a higher incidence in immunocompromised individuals (those receiving immunosuppressive therapy, organ transplants, and HIV / AIDS treatment) and in individuals with certain autoimmune disorders. However, the above conditions and factors are relatively rare in the general population and may explain only a small proportion of NHL cases.

Epidemiological studies

Epidemiological studies suggest that some environmental and occupational exposure and lifestyle factors may be associated with NHL risk. Smoking increases the risk of follicular lymphoma, which is especially true in the case of current smokers compared to former smokers​2​. Alcohol consumption was reported to be associated with a lower risk of NHL and had the least protective effect against Burkitt’s lymphoma​3​. An increased risk of FL and chronic lymphocytic leukemia / small lymphocytic lymphoma (CLL / SLL) has been reported in women who started using hair dye before 1980​4​.

Prospective studies

A meta-analysis of prospective studies has shown a positive association between BMI and the risk of diffuse large B-cell lymphoma (DLBCL)​5​. Moreover, exposure to organic solvents at work is thought to be associated with an increased risk of NHL​6​. Several studies have also looked at dietary intake and the risk of NHL. While high consumption of protein and fat is associated with an increased risk of NHL, high fruit and vegetable consumption is reported to be associated with a lower risk of NHL​7,8​.

Genetic and genomic risk factors

There is growing evidence of genetic polymorphisms associated with increased NHL risk​9​. Furthermore, studies have reported that some polymorphisms in the Th1 / Th2 cytokine pathway genes (IL10 and TNF) increase the risk of B-cell lymphoma compared to control groups​10​. Studies have also reported that toll-like receptor genes, such as TLR2 and TLR4, are associated with a risk of NHL subtypes​11​. A hospital study examined polymorphisms in 12 genes (TRAF1, BAT2, RIPK3, TLR6, DUSP2, MAP3K5, CREB1, SELPLG, B3GNT3, LSP1, ITGB3, FGG) that are associated with NHL risk​12​.

Single Nucleotide Polymorphisms

Several epidemiological studies have reported an increased risk of NHL associated with single nucleotide polymorphisms in the GPX1, SOD2, NOS2A, CYBA, and AKR1A1 genes​13,14​.

Chromosome translocations of t (3,22) translocation of DLBCL and the t (14,18) translocation of FL are characteristic of NHL​15​. Polymorphisms in DNA repair genes may alter repair ability and alter NHL risk. Several population-based case-controlled studies have shown an increased risk of NHL associated with genetic polymorphisms in DNA repair genes, including ERCC5, RAG1, WRN, LIG4, XRCC1, and MGMT​16​.

Several epidemiologic studies reported an increased risk of NHL associated with SNPs (single nucleotide polymorphisms) in genes of GPX1, NOS2A, SOD2, AKR1A1, and CYBA​16​.

Various Chromosomal translocations, such as t(3, 22) translocation in DLBCL and t(14,18) translocation in FL, are a hallmark of NHL. Polymorphisms in DNA repair genes may modify repair capacity and alter the risk of NHL. Several population-based case-control studies have found an increased risk of NHL associated with genetic polymorphisms in DNA repair genes, including RAG1, LIG4, ERCC5, WRN, MGMT, and XRCC1​16​.


  1. 1.
    Eltom M, Jemal A, Mbulaiteye S, Devesa S, Biggar R. Trends in Kaposi’s sarcoma and non-Hodgkin’s lymphoma incidence in the United States from 1973 through 1998. J Natl Cancer Inst. 2002;94(16):1204-1210. doi:10.1093/jnci/94.16.1204
  2. 2.
    Morton L, Hartge P, Holford T, et al. Cigarette smoking and risk of non-Hodgkin lymphoma: a pooled analysis from the International Lymphoma Epidemiology Consortium (interlymph). Cancer Epidemiol Biomarkers Prev. 2005;14(4):925-933. doi:10.1158/1055-9965.EPI-04-0693
  3. 3.
    Morton L, Zheng T, Holford T, et al. Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis. Lancet Oncol. 2005;6(7):469-476. doi:10.1016/S1470-2045(05)70214-X
  4. 4.
    Zhang Y, Sanjose S, Bracci P, et al. Personal use of hair dye and the risk of certain subtypes of non-Hodgkin lymphoma. Am J Epidemiol. 2008;167(11):1321-1331. doi:10.1093/aje/kwn058
  5. 5.
    Larsson S, Wolk A. Body mass index and risk of non-Hodgkin’s and Hodgkin’s lymphoma: a meta-analysis of prospective studies. Eur J Cancer. 2011;47(16):2422-2430. doi:10.1016/j.ejca.2011.06.029
  6. 6.
    Dryver E, Brandt L, Kauppinen T, Olsson H. Occupational exposures and non-Hodgkin’s lymphoma in Southern Sweden. Int J Occup Environ Health. 2004;10(1):13-21. doi:10.1179/oeh.2004.10.1.13
  7. 7.
    Chang E, Bälter K, Torrång A, et al. Nutrient intake and risk of non-Hodgkin’s lymphoma. Am J Epidemiol. 2006;164(12):1222-1232. doi:10.1093/aje/kwj330
  8. 8.
    Zheng T, Holford T, Leaderer B, et al. Diet and nutrient intakes and risk of non-Hodgkin’s lymphoma in Connecticut women. Am J Epidemiol. 2004;159(5):454-466. doi:10.1093/aje/kwh067
  9. 9.
    Skibola C, Nieters A, Bracci P, et al. A functional TNFRSF5 gene variant is associated with risk of lymphoma. Blood. 2008;111(8):4348-4354. doi:10.1182/blood-2007-09-112144
  10. 10.
    Rothman N, Skibola C, Wang S, et al. Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium. Lancet Oncol. 2006;7(1):27-38. doi:10.1016/S1470-2045(05)70434-4
  11. 11.
    Nieters A, Beckmann L, Deeg E, Becker N. Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk. Genes Immun. 2006;7(8):615-624. doi:10.1038/sj.gene.6364337
  12. 12.
    Cerhan J, Ansell S, Fredericksen Z, et al. Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma. Blood. 2007;110(13):4455-4463. doi:10.1182/blood-2007-05-088682
  13. 13.
    Lan Q, Zheng T, Shen M, et al. Genetic polymorphisms in the oxidative stress pathway and susceptibility to non-Hodgkin lymphoma. Hum Genet. 2007;121(2):161-168. doi:10.1007/s00439-006-0288-9
  14. 14.
    Lightfoot T, Skibola C, Smith A, et al. Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin’s lymphoma. Haematologica. 2006;91(9):1222-1227. https://www.ncbi.nlm.nih.gov/pubmed/16956821
  15. 15.
    Chaganti R, Nanjangud G, Schmidt H, Teruya-Feldstein J. Recurring chromosomal abnormalities in non-Hodgkin’s lymphoma: biologic and clinical significance. Semin Hematol. 2000;37(4):396-411. doi:10.1016/s0037-1963(00)90019-2
  16. 16.
    Shen M, Purdue M, Kricker A, et al. Polymorphisms in DNA repair genes and risk of non-Hodgkin’s lymphoma in New South Wales, Australia. Haematologica. 2007;92(9):1180-1185. doi:10.3324/haematol.11324