New insights into the epidemiology of non-Hodgkin lymphoma and implications for therapy

Abstract

Non-Hodgkin lymphoma (NHL) comprises numerous biologically and clinically heterogeneous subtypes, with limited data examining the risk factors for these distinct disease entities. Many limitations exist when studying lymphoma epidemiology; therefore, until recently, little was known regarding the etiology of NHL subtypes. This review highlights the results of recent pooled analyses examining the risk factors for NHL subtypes. We outline the heterogeneity and commonality among the risk factors for NHL subtypes, with proposed subtype-specific as well as shared etiologic mechanisms. In addition, we describe how the study of lymphoma epidemiology may translate into prevention or therapeutic targeting as we continue to explore the complexities of lifestyle and genetic factors that impact lymphomagenesis.

Keywords:

• epidemiology
• non-Hodgkin lymphoma
• risk factors

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Pooled case–control analyses from the InterLymph non-Hodgkin lymphoma (NHL) Subtypes Project have identified a number of medical history, family history, lifestyle and occupational associations with NHL subtypes.

• There is variation in diffuse large B-cell lymphoma (DLBCL) risk and preventive factors according to sex and anatomical site of the disease.

• Differences in sporadic Burkitt lymphoma (BL) risk factors between younger and older populations suggest that etiology of this disease may vary with age.

• Cigarette smoking has been found to be associated with follicular lymphoma (FL) in other studies. The results from the InterLymph NHL Subtypes Project for FL suggest that this risk factor may be more prominent in females.

• T-cell NHL subtypes are more strongly associated with T-cell activating autoimmune diseases such as celiac disease, cigarette smoking and eczema.

• B-cell NHL subtypes are more strongly associated with B-cell activating autoimmune diseases such as systemic lupus erythematosus, HCV infection and history of blood transfusion.

• Three distinct subgroups of NHL can be identified based on the similarities of risk and preventive factors: peripheral T-cell lymphoma and mycosis fungoides/Sezary syndrome; marginal zone lymphoma and BL; and DLBCL, FL, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), mantle cell lymphoma and lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia.

• DLBCL, CLL/SLL, and lymphoplasmacytic lymphoma/Waldenström’s macroglobulinemia show a significantly different risk profile from FL and mantle cell lymphoma, with the key differentiating risk factors of B-cell activating autoimmune diseases, hay fever, allergy, alcohol consumption, HCV seropositivity, cigarette smoking and occupation as a teacher or a general farm worker.

• The highest quartile of sun exposure is associated with decreased risk of DLBCL, FL, CLL/SLL and anaplastic large cell lymphoma, suggesting a possible role for vitamin D deficiency or sunlight-mediated immune modulation in non-Hodgkin lymphomagenesis.

• Identifying the NHL risk factors may lead to discovery of disease etiology as well as preventive and therapeutic targets.