A systematic review and meta-analysis of glyphosate based herbicide exposure and risk of nonHodgkin's lymphoma

BackgroundGlyphosate-based herbicides are among the most widely used agricultural chemicals globally. Concerns regarding their carcinogenic potential, particularly in relation to non-Hodgkins lymphoma (NHL), persist despite multiple prior systematic reviews and meta-analyses. However, these reviews have demonstrated important methodological limitations and inconsistent analytic decisions, limiting confidence in their conclusions. ObjectiveTo conduct a rigorous, up-to-date systematic review and meta-analysis of observational studies examining the association between glyphosate-based herbicide exposure and risk of NHL and its subtypes, while addressing methodological and analytic shortcomings of prior syntheses. MethodsWe searched MEDLINE (1970-February 26, 2026) and EMBASE (inception-February 26, 2026), supplemented by reference list review. Eligible studies included cohort, case-control, and pooled analyses reporting effect estimates (or sufficient data) for glyphosate exposure and NHL incidence. Two reviewers independently assessed risk of bias using the Newcastle-Ottawa Scale (for primary studies) and structured criteria for pooled analyses. Random- and fixed-effects meta-analyses were conducted using inverse-variance methods. Heterogeneity was evaluated using Cochrans Q and I{superscript 2} statistics. Publication bias was assessed using standard and contour-enhanced funnel plots. Sensitivity analyses addressed overlapping cohorts, hazard ratio inclusion, exposure definitions, and model overfitting (events-per-variable considerations). Certainty of evidence was graded using GRADE. ResultsSeventeen publications were identified, representing 20 unique study populations; after accounting for overlap, 10 primary datasets were included in quantitative synthesis. Five studies were assessed as low risk of bias, four as moderate risk, and one as high risk. For ever exposure, the random-effects model across all eligible datasets yielded an odds ratio (OR) of 1.11 (95% CI: 0.98-1.27), with moderate heterogeneity (I{superscript 2}{approx}53%). In sensitivity analyses excluding hazard ratio-only studies and overlapping cohorts, pooled ORs ranged from 1.19 to 1.23, with estimates approaching or reaching statistical significance depending on modeling assumptions. For the highest exposure categories, the random-effects model demonstrated a statistically significant association (OR{approx}1.38; 95% CI: 1.00-1.90), with moderate heterogeneity (I{superscript 2}{approx}61%). Sensitivity analyses excluding selected pooled cohort estimates strengthened the association (OR{approx}1.47; 95% CI: 1.04-2.06). Analyses incorporating alternative cumulative exposure metrics yielded similar significant associations (OR{approx}1.33-1.45) with low or absent residual heterogeneity. Subtype analyses suggested elevated risks particularly for diffuse large B-cell lymphoma and follicular lymphoma in certain datasets. Publication bias assessments revealed evidence of small-study effects in some models, though contour-enhanced analyses suggested that not all asymmetry was attributable to selective publication. Overall certainty of evidence was graded as moderate for highest exposure analyses and low-to-moderate for ever-exposure analyses due to residual heterogeneity and observational design limitations. ConclusionsThis updated synthesis indicates that while associations with ever exposure to glyphosate are modest and sensitive to analytic decisions, higher levels of exposure are consistently associated with increased odds of NHL. Findings are robust across multiple sensitivity analyses addressing overlapping data, exposure classification, and model overfitting. These results support a dose-related association between glyphosate-based herbicide exposure and NHL risk and underscore the need for continued surveillance, improved exposure characterization, and prospective cohort analyses with minimized loss to follow-up and transparent analytic reporting.