Non-Hodgkin lymphoma causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Preeti Singh, M.B.B.S.[2]


Non Hodgkin lymphoma may arise due to genetic causes, immunodeficiency state, infection, environmental factor, and chronic inflammation.


Life-threatening Causes

  • There are no life-threatening causes of non Hodgkin lymphoma (NHL), however complications resulting from untreated non Hodgkin lymphoma is common.

Common Causes

Common causes of non Hodgkin lymphoma may include:

Chromosomal Translocation

  • Chromosomal translocations play a vital role in the pathogenesis of many lymphomas.[1]
  • The t(14;18)(q32;q21) translocation is the most common chromosomal abnormality associated with Non Hodgkin Lymphoma.
  • It occurs in 85% of follicular lymphomas and 28% of higher-grade Non Hodgkin Lymphoma.[2]
  • This results in the juxtaposition of the bcl -2 apoptotic inhibitor oncogene at chromosome band 18q21 to the heavy chain region of the immunoglobulin (Ig) locus within chromosome band 14q32..
  • The t(11;14)(q13;q32) translocation has association with mantle cell lymphoma.[3]
  • It causes overexpression of bcl -1 (cyclin D1/PRAD 1), a cell-cycle regulator on chromosome band 11q13.[4]
  • The 8q24 translocations causes c-myc dysregulation.[5][6]
  • It is frequently seen in high-grade small noncleaved lymphomas such as Burkitt lymphoma, including the one associated with HIV infection.
  • The t(2;5)(p23;q35) translocation occurs between the nucleophosmin (NPM) gene and the anaplastic lymphoma kinase (ALK1) gene.[4][7]
  • This results in the expression of a fusion protein found in a majority of anaplastic large cell lymphomas.
  • Two chromosomal translocations, t(11;18)(q21;q21) and t(1;14)(p22;132), are associated with mucosa-associated lymphoid tissue (MALT) lymphomas.
  • The more common type such as t[11;18][q21;q21] translocates the apoptosis inhibitor AP12 gene with the MALT1 gene; resulting in the expression of an aberrant fusion protein.
  • The other translocation, t(1;14)(p22;132), involves the translocation of the bcl -10 gene to the immunoglobulin gene enhancer region.


  • Some viruses are involved in the pathogenesis of Non Hodgkin Lymphoma because of their ability to induce chronic antigenic stimulation and cytokine dysregulation resulting in uncontrolled B- or T-cell stimulation, proliferation, and lymphomagenesis.
  • Epstein-Barr virus (EBV) is a DNA virus that is associated with Burkitt lymphoma, lymphomas in immunocompromised patients; and sinonasal lymphoma.
  • Human T-cell leukemia virus type 1 (HTLV-1) causes a latent infection due to reverse transcription ability in activated T-helper cells.
  • It is endemic in certain areas of Japan and the Caribbean islands, and approximately 5% of carriers develop adult T-cell leukemia or lymphoma.
  • Hepatitis C virus (HCV) is associated with the development of clonal B-cell expansions, lymphoplasmacytic lymphoma; and Waldenström macroglobulinemia especially in the setting of essential mixed cryoglobulinemia.
  • Kaposi sarcoma–associated herpesvirus (KSHV) is associated with body cavity lymphomas in patients with immunocompromised state and in patients with multicentric Castleman disease.
  • Helicobacter pylori infection is associated with the development of gastrointestinal lymphomassuch as gastric mucosa-associated lymphoid tissue (MALT) lymphomas.

Environmental Factors

Environmental factors associated with Non Hodgkin Lymphoma include:[8][9]

  • Pesticides
  • Herbicides
  • Solvents
  • Organic chemicals
  • Wood preservatives
  • Dusts
  • Hair dye
  • Chemotherapy
  • Radiation exposure
  • Smoking

Immunodeficiency States

Immunodeficiency states associated with Non Hodgkin Lymphoma include:[2]

  • Congenital immunodeficiency states
    • Severe combined immunodeficiency disease (SCID)
    • Wiskott-Aldrich syndrome
  • Acquired immunodeficiency states
    • AIDS
  • Induced immunodeficiency states
    • Immunosuppression

Chronic Inflammation

Autoimmune disorders associated with Non Hodgkin Lymphoma include:[10][11]

  • Sjögren syndrome
  • Hashimoto thyroiditis
  • Celiac disease

Causes by Organ System

Cardiovascular No underlying causes
Chemical/Poisoning No underlying causes
Dental No underlying causes
Dermatologic No underlying causes
Drug Side Effect No underlying causes
Ear Nose Throat No underlying causes
Endocrine No underlying causes

Pesticides, Herbicides, Solvents, Organic chemicals, Wood preservatives, Dusts, Hair dye, Chemotherapy, Radiation exposure; and Smoking.

Gastroenterologic No underlying causes
Genetic Severe combined immunodeficiency disease and Wiskott-Aldrich syndrome; and Human T-cell leukemia virus type 1.
Hematologic No underlying causes
Iatrogenic No underlying causes
Infectious Disease AIDS, Epstein-Barr virus, Hepatitis C virus, Kaposi sarcoma–associated herpesvirus; and Helicobacter pylori.
Musculoskeletal/Orthopedic No underlying causes
Neurologic No underlying causes
Nutritional/Metabolic No underlying causes
Obstetric/Gynecologic No underlying causes
Oncologic No underlying causes
Ophthalmologic No underlying causes
Overdose/Toxicity No underlying causes
Psychiatric No underlying causes
Pulmonary No underlying causes
Renal/Electrolyte No underlying causes
Rheumatology/Immunology/Allergy Sjögren syndrome, Hashimoto thyroiditis; and Celiac disease.
Sexual No underlying causes
Trauma No underlying causes
Urologic No underlying causes
Miscellaneous No underlying causes

Causes in Alphabetical Order

List the causes of the disease in alphabetical order:

  • AIDS
  • Celiac disease
  • Chemotherapy
  • Dusts
  • Epstein-Barr virus
  • Hair dye
  • Hashimoto thyroiditis
  • Helicobacter pylori
  • Hepatitis C virus
  • Herbicides
  • Human T-cell leukemia virus type 1
  • Kaposi sarcoma–associated herpesvirus
  • Organic chemicals
  • Pesticides
  • Radiation exposure
  • Severe combined immunodeficiency disease
  • Sjögren syndrome
  • Smoking
  • Solvents
  • Wiskott-Aldrich syndrome
  • Wood preservatives


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  2. 2.0 2.1 Crump C, Sundquist J, Sieh W, Winkleby MA, Sundquist K (2014). "Season of birth and risk of Hodgkin and non-Hodgkin lymphoma". Int J Cancer. 135 (11): 2735–9. doi:10.1002/ijc.28909. PMC 4165654. PMID 24752499.
  3. Morton LM, Zheng T, Holford TR, Holly EA, Chiu BC, Costantini AS; et al. (2005). "Alcohol consumption and risk of non-Hodgkin lymphoma: a pooled analysis". Lancet Oncol. 6 (7): 469–76. doi:10.1016/S1470-2045(05)70214-X. PMID 15992695.
  4. 4.0 4.1 Wang SS, Flowers CR, Kadin ME, Chang ET, Hughes AM, Ansell SM; et al. (2014). "Medical history, lifestyle, family history, and occupational risk factors for peripheral T-cell lymphomas: the InterLymph Non-Hodgkin Lymphoma Subtypes Project". J Natl Cancer Inst Monogr. 2014 (48): 66–75. doi:10.1093/jncimonographs/lgu012. PMC 4155466. PMID 25174027.
  5. Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R; et al. (2016). "The 2016 revision of the World Health Organization classification of lymphoid neoplasms". Blood. 127 (20): 2375–90. doi:10.1182/blood-2016-01-643569. PMC 4874220. PMID 26980727.
  6. Matutes E (2018). "The 2017 WHO update on mature T- and natural killer (NK) cell neoplasms". Int J Lab Hematol. 40 Suppl 1: 97–103. doi:10.1111/ijlh.12817. PMID 29741263.
  7. Morton LM, Slager SL, Cerhan JR, Wang SS, Vajdic CM, Skibola CF; et al. (2014). "Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: the InterLymph Non-Hodgkin Lymphoma Subtypes Project". J Natl Cancer Inst Monogr. 2014 (48): 130–44. doi:10.1093/jncimonographs/lgu013. PMC 4155467. PMID 25174034.
  8. Antonopoulos CN, Sergentanis TN, Papadopoulou C, Andrie E, Dessypris N, Panagopoulou P; et al. (2011). "Maternal smoking during pregnancy and childhood lymphoma: a meta-analysis". Int J Cancer. 129 (11): 2694–703. doi:10.1002/ijc.25929. PMID 21225624.
  9. Dikalioti SK, Chang ET, Dessypris N, Papadopoulou C, Skenderis N, Pourtsidis A; et al. (2012). "Allergy-associated symptoms in relation to childhood non-Hodgkin's as contrasted to Hodgkin's lymphomas: a case-control study in Greece and meta-analysis". Eur J Cancer. 48 (12): 1860–6. doi:10.1016/j.ejca.2011.12.010. PMID 22230747.
  10. Wang SS, Vajdic CM, Linet MS, Slager SL, Voutsinas J, Nieters A; et al. (2015). "Associations of non-Hodgkin Lymphoma (NHL) risk with autoimmune conditions according to putative NHL loci". Am J Epidemiol. 181 (6): 406–21. doi:10.1093/aje/kwu290. PMC 4402340. PMID 25713336.
  11. Fallah M, Liu X, Ji J, Försti A, Sundquist K, Hemminki K (2014). "Autoimmune diseases associated with non-Hodgkin lymphoma: a nationwide cohort study". Ann Oncol. 25 (10): 2025–30. doi:10.1093/annonc/mdu365. PMID 25081899.