Genetic polymorphisms of tumor necrosis factor receptor-associated factor 3 and their association with acute lymphoblastic leukemia.
PMID 41619431 | DOI 10.1016/j.cancergen.2026.01.012 · Cancer genetics · 2026
BACKGROUND: Acute lymphoblastic leukemia (ALL) is an aggressive hematological malignancy driven by genetic and immunological dysregulation. Tumor necrosis factor receptor-associated factor 3 (TRAF3) plays an essential role in regulating immune signaling, lymphocyte homeostasis, and NF-κB pathways. Although TRAF3 alterations have been implicated in various immune disorders and hematologic cancers, the contribution of TRAF3 genetic polymorphisms to ALL susceptibility remains insufficiently understood. PURPOSE: To investigate the association between three TRAF3 single nucleotide polymorphisms (SNPs); rs33980500, rs13210247, and rs1131877, and ALL susceptibility in Saudi patients, and to evaluate TRAF3 mRNA expression levels in ALL compared to healthy individuals. METHODS: A case-control study was conducted involving 150 newly diagnosed ALL patients and 115 age- and sex-matched healthy controls. Genotyping of the selected TRAF3 SNPs was performed using TaqMan allelic discrimination assays. TRAF3 mRNA expression in peripheral blood white cells was quantified through RT-qPCR. Statistical analyses included genotype/allele frequency comparisons, odds ratios, Hardy-Weinberg equilibrium testing, linkage disequilibrium assessment, and haplotype construction. RESULTS: None of the analyzed SNPs showed a statistically significant association with ALL across genotype, allele, or haplotype models. Linkage disequilibrium between the SNPs was absent. However, TRAF3 mRNA expression was significantly upregulated in ALL patients, exhibiting a 3.88-fold increase compared with controls (p < 0.05). CONCLUSION: Although the examined TRAF3 SNPs were not associated with ALL susceptibility in this cohort, the marked elevation of TRAF3 mRNA expression suggests a potential role for TRAF3-related signaling in ALL pathogenesis. TRAF3 expression may represent a promising biomarker warranting further investigation.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | TRAF3 | “Tumor necrosis factor receptor-associated factor 3 (TRAF3) plays an essential role in regulating immune signaling, lymphocyte homeostasis, and NF-κB pathways.” | 0.98 | hgnc_dict_v1 |
| phenotype | leukemia | “Genetic polymorphisms of tumor necrosis factor receptor-associated factor 3 and their association with acute lymphoblastic leukemia.” | 0.98 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “PURPOSE: To investigate the association between three TRAF3 single nucleotide polymorphisms (SNPs); rs33980500, rs13210247, and rs1131877, and ALL susceptibility in Saudi patients, and to evaluate TRAF3 mRNA expression levels in ALL compared to healthy individuals. METHODS: A case-control study was conducted involving 150 newly diagnosed ALL patients and 115 age- and sex-matched healthy controls.” | 0.95 | saudi_context_rules_v1 |
| variant | rs33980500 | “PURPOSE: To investigate the association between three TRAF3 single nucleotide polymorphisms (SNPs); rs33980500, rs13210247, and rs1131877, and ALL susceptibility in Saudi patients, and to evaluate TRAF3 mRNA expression levels in ALL compared to healthy individuals.” | 0.90 | hgvs_regex_v1 |
| variant | rs13210247 | “PURPOSE: To investigate the association between three TRAF3 single nucleotide polymorphisms (SNPs); rs33980500, rs13210247, and rs1131877, and ALL susceptibility in Saudi patients, and to evaluate TRAF3 mRNA expression levels in ALL compared to healthy individuals.” | 0.90 | hgvs_regex_v1 |
| variant | rs1131877 | “PURPOSE: To investigate the association between three TRAF3 single nucleotide polymorphisms (SNPs); rs33980500, rs13210247, and rs1131877, and ALL susceptibility in Saudi patients, and to evaluate TRAF3 mRNA expression levels in ALL compared to healthy individuals.” | 0.90 | hgvs_regex_v1 |