ABSTRACT
It is well established that the male sex is associated with increased risk for, as well as poorer survival of, most cancers. A similar pattern has been described in lymphomas but has not yet been comprehensively assessed. In this nationwide population-based cohort study, we used the Swedish Lymphoma Register to investigate sex differences in lymphoma subtype incidence and excess mortality in adults (age 18-99) diagnosed in 2000-2019. Male-to-female incidence rate ratios (IRRs) and excess mortality ratios (EMRs) adjusted for age and calendar year were predicted using Poisson regression. We identified 36 795 lymphoma cases, 20 738 (56.4%) in men and 16 057 (43.6%) in women. Men were at significantly higher risk of 14 out of 16 lymphoma subtypes with IRRs ranging from 1.15 (95% confidence interval [CI] 1.09-1.22) in follicular lymphoma to 5.95 (95% CI 4.89-7.24) in hairy cell leukemia. EMRs >1 were seen in 13 out of 16 lymphoma subtypes indicating higher mortality in men, although only statistically significant for classical Hodgkin lymphoma 1.26 (95% CI 1.04-1.54), aggressive lymphoma not otherwise specified 1.29 (95% CI 1.08-1.55), and small lymphocytic lymphoma 1.52 (95% CI 1.11-2.07). A corresponding analysis using data from the Danish Lymphoma Register was performed with comparable results. In conclusion, we demonstrate a significantly higher incidence and trend toward higher mortality in men for most lymphoma subtypes. Future studies with large patient material that include detailed clinicopathological prognostic factors are warranted to further delineate and explain sex differences in lymphoma survival to enable optimal management of lymphoma patients regardless of sex.
Subject(s)
Leukemia, Lymphocytic, Chronic, B-Cell , Lymphoma, Follicular , Adult , Humans , Female , Male , Adolescent , Young Adult , Middle Aged , Aged , Aged, 80 and over , Incidence , Cohort Studies , Sex CharacteristicsSubject(s)
Multiple Myeloma/epidemiology , Smoldering Multiple Myeloma/pathology , Adult , Aged , Aged, 80 and over , Biomarkers , Biomarkers, Tumor , Bone Marrow/pathology , Disease Progression , Female , Follow-Up Studies , Humans , Immunoglobulin kappa-Chains/blood , Immunoglobulin lambda-Chains/blood , Male , Middle Aged , Models, Biological , Myeloma Proteins/analysis , Plasma Cells/pathology , Proportional Hazards Models , ROC Curve , Risk , Risk Assessment , Severity of Illness Index , Smoldering Multiple Myeloma/bloodABSTRACT
Type 1 diabetes mellitus (T1D) is a chronic autoimmune disease characterized by beta cell destruction, insulin deficiency and hyperglycemia. Activated macrophages and autoimmune T cells play a crucial role in the pathogenesis of hyperglycemia in NOD murine diabetes models, but the molecular mechanisms of macrophage activation are unknown. We recently identified pigment epithelium-derived factor (PEDF) as an adipocyte-derived factor that activates macrophages and mediates insulin resistance. Reasoning that PEDF might participate as a proinflammatory mediator in murine diabetes, we measured PEDF levels in NOD mice. PEDF levels are significantly elevated in pancreas, in correlation with pancreatic TNF levels in NOD mice. To identify experimental therapeutics, we screened 2,327 compounds in two chemical libraries (the NIH Clinical Collection and Pharmakon-1600a) for leads that inhibit PEDF mediated TNF release in macrophage cultures. The lead molecule selected, "emetine" is a widely used emetic. It inhibited PEDF-mediated macrophage activation with an EC50 or 146 nM. Administration of emetine to NOD mice and to C57Bl6 mice subjected to streptozotocin significantly attenuated hyperglycemia, reduced TNF levels in pancreas, and attenuated insulitis. Together, these results suggest that targeting PEDF with emetine may attenuate TNF release and hyperglycemia in murine diabetes models. This suggests that further investigation of PEDF and emetine in the pathogenesis of human diabetes is warranted.
