ArticleCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology2025
Evaluation of Etiologic Heterogeneity for Risk of Diffuse Large B-Cell Lymphoma Subtype Defined by the Cell of Origin.
Article in Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundDiffuse large B-cell lymphoma (DLBCL) is clinically heterogeneous, and gene expression profiling has identified at least two biologically distinct DLBCL subtypes defined by their cell of origin (COO): germinal center B cell (GCB) and activate B cell (ABC) or non-GCB. We evaluated a variety of putative DLBCL risk factors for etiologic heterogeneity by the COO in a clinic-based study of newly diagnosed DLBCL cases (N = 638) and frequency-matched controls (N = 2,253).
methodsThe COO was determined on formalin-fixed, paraffin-embedded tumor tissue, with DLBCL classified as GCB (N = 283), non-GCB (N = 188), or undetermined/missing (N = 167; mainly because of lack of tissue). Multivariable logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).
resultsWe identified heterogeneity by the COO for low socioeconomic status (SES), which was only associated with non-GCB DLBCL (OR = 1.88 for low vs. average SES; 95% CI, 1.08-3.27); alcohol use, which was only associated with GCB DLBCL (OR = 0.48 for former drinkers; 95% CI, 0.29-0.80 and OR = 0.47 for current drinkers; 95% CI, 0.32-0.71); and borderline heterogeneity for the regular use of regular/extra-strength aspirin, which was only associated with non-GCB DLBCL (OR = 0.36; 95% CI, 0.16-0.85). In contrast, there was no significant heterogeneity by the COO for family history, medical history, or other lifestyle factors.
conclusionsAlthough requiring confirmation, most risk factors for DLBCL did not show etiologic heterogeneity by the COO, with some notable exceptions including alcohol use, SES, and perhaps regular use of regular/extra-strength aspirin showing associations. IMPACT: Mechanistically, these findings suggest that most of the DLBCL risk factors evaluated here influence lymphomagenesis prior to differentiation into COO subtypes, with selected factors acting later.
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