Risk Factors for Marginal Zone Lymphoma (MZL)

The etiology of MZL is poorly understood; however, it has been suggested that certain infections and autoimmune disorders may affect the likelihood that a person will develop MZL.1


Hepatitis C virus is associated with ~30% of all MZLs (primarily splenic MZL) and ~35% of patients with non-gastric MALT and may indirectly contribute to the pathogenesis of lymphoma by over-stimulating the immune system.1,2 H. pylori infection plays a critical role in the pathogenesis of gastric MALT lymphomas.1

Autoimmune Disorders

Some autoimmune disorders cause chronic inflammation, which may contribute to the development of lymphoma. For example, Sjögren’s syndrome, Hashimoto’s thyroiditis, rheumatoid arthritis, and systemic lupus erythematosus are all linked to an increased risk of developing MZL subtypes.2

Additional Risk Factors that May Increase the Risk of Developing NHL3,4:

  • Immunologic factors, including immunodeficiency, infection with human immunodeficiency virus (HIV), and genetic disorders that cause weakened immune function (primary immunodeficiency)
  • Autoimmune disorders lead to overactivity of the immune system which can make lymphocytes grow and divide more than normal, increasing the opportunity for lymphoma-causing mutations to arise
  • Some infections, in particular, viruses that can directly alter the DNA of lymphocytes, such as Epstein-Barr virus (EBV), human T-lymphotropic virus 1 (HTLV-1), and human herpes virus 8 (HHV-8)
  • Patients have an increased risk of NHL if they have a first degree relative (parent, child, sibling) with a history of NHL
  • Prior cancer therapy
  • Chemical or environmental exposure
  • Lifestyle factors, including smoking, diet, and obesity

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for B-Cell Lymphomas V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed July 10, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2. Lymphoma Action. Causes of lymphoma. https://lymphoma-action.org.uk/about-lymphoma-what-lymphoma/causes-lymphoma. Accessed February 7, 2019. 3. Merck Manual. 20th ed. Lane KAG, ed. Rahway, New Jersey: Merck & Co., Inc. 2018. 4. American Cancer Society. Non-Hodgkin Lymphoma Risk Factors. https://www.cancer.org/cancer/non-hodgkin-lymphoma/causes-risks-prevention/risk-factors.html. Accessed June 14, 2019.