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]

## Overview

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

## Causes

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### Life-threatening Causes

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

### Common Causes

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Common causes of non Hodgkin lymphoma may include:

* Chromosomal translocation
* Infections
* Environmental factor
* Immunodeficiency state
* Chronic inflammation

#### Chromosomal Translocation

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* 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.

#### Infection

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* 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

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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

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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

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

* Sjögren syndrome
* Hashimoto thyroiditis
* Celiac disease

### Causes by Organ System

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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
Environmental |

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

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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

## References

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1. ↑ Chang ET, Smedby KE, Hjalgrim H, Porwit-MacDonald A, Roos G, Glimelius B; et al. (2005). "Family history of hematopoietic malignancy and risk of lymphoma". J Natl Cancer Inst. 97 (19): 1466–74. doi:10.1093/jnci/dji293. PMID 16204696.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
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.CS1 maint: Multiple names: authors list (link)