Non-Hodgkin lymphoma causes

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.

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

Common causes of non Hodgkin lymphoma may include:

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

• 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 associated with Non Hodgkin Lymphoma include:^[8][9]

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

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

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

• Sjögren syndrome
• Hashimoto thyroiditis
• Celiac disease

List the causes of the disease in alphabetical order: