The TNFRSF13B gene encodes the receptor TACI, which regulates B‑cell survival and immune homeostasis. While pathogenic TNFRSF13B variants have been implicated in primary immunodeficiency, their contribution to lymphoma susceptibility has not been clearly established. This study evaluated whether the TNFRSF13B polymorphism rs4792800 (A>G) alters lymphoma risk and explored potential regulatory mechanisms linking the variant to B‑cell biology.
Investigators performed a hospital‑based case‑control study comprising 200 histologically confirmed lymphoma patients and 119 healthy control subjects. Patient and control demographics were accounted for in adjusted analyses (logistic regression adjusted for age and sex). The primary genetic exposure was rs4792800 genotype determined by allele‑specific PCR.
Genotyping of rs4792800 used allele‑specific PCR. Associations between rs4792800 and lymphoma were estimated with logistic regression producing odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age and sex. The authors applied stratified analyses by lymphoma subtype, by cell lineage (B‑cell versus T‑cell), and by Epstein‑Barr virus (EBV) status. Multiple comparisons were addressed using false discovery rate (FDR) correction; reported q values reflect this adjustment.
Allelic comparison showed the G allele was more common in lymphoma cases than controls (51.8% vs 42.0%), yielding an allelic OR of 1.48 (95% CI 1.07–2.06, p = 0.018, q = 0.036). Under a recessive model, individuals with the GG genotype had an increased lymphoma risk (OR 1.9, 95% CI 1.06–3.43, p = 0.031, q = 0.042).
Subtype analysis identified a stronger association for diffuse large B‑cell lymphoma (DLBCL) (OR 2.32, 95% CI 1.21–4.47, q = 0.036). An exploratory association was observed for T‑cell lymphoma (OR 3.16, 95% CI 1.12–8.90, q = 0.087), but the authors note that this finding requires independent validation given the exploratory nature and wider CI.
When stratified by EBV status, the rs4792800‑associated risk was significant among EBV‑negative patients (OR 1.99, q = 0.049). The smaller EBV‑positive subgroup did not show a statistically significant association in this dataset.
Computational analyses placed rs4792800 within a B‑cell‑specific enhancer element. Motif disruption predictions indicated that the G allele leads to a loss of an EBF1 binding motif (approximately 25.6% loss) while increasing predicted binding for PAX5 (approximately 17.9% gain). Based on these in silico results, the authors infer that the G allele would reduce TNFRSF13B transcription and consequently lower TACI protein levels in B cells.
These predicted regulatory effects provide a plausible mechanistic link between the inherited variant and impaired TACI‑mediated immune surveillance, which could facilitate lymphomagenesis independently of viral oncogenic mechanisms such as EBV.
In this case‑control series, the rs4792800 GG genotype in TNFRSF13B was associated with increased overall lymphoma risk, with the strongest signal seen for DLBCL and for EBV‑negative disease. The authors propose that inherited disruption of a B‑cell enhancer and consequent decrease in TACI expression may reduce immune surveillance and predispose to lymphoma. The observed association with T‑cell lymphoma was reported as exploratory and in need of replication. The study used FDR correction for multiple testing and adjusted for age and sex in regression models.
Keywords reported by the authors include EBV‑negative lymphoma, gene‑association study, lymphoma susceptibility, TNFRSF13B, and rs4792800. Publication metadata in the source report the article in Gene (2026), PMID 42114689, DOI 10.1016/j.gene.2026.150200. Authors and institutional affiliations are provided in the source.
The authors declared no known competing financial interests or personal relationships that could have influenced the work.
Note: Details beyond the abstract (for example, full demographic breakdowns, laboratory validation of expression changes, or independent replication cohorts) were not reported in the provided source text and therefore are not described here.