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Associations of genetically predicted interleukin-6 and tumor necrosis factor signaling pathways with mortality among persons with colorectal cancer: a two-sample Mendelian randomization - PubMed

3 days ago
  • #colorectal-cancer
  • #inflammation
  • #Mendelian-randomization
  • Study investigates associations between genetically predicted IL-6 and TNF-α signaling pathways and mortality in colorectal cancer (CRC) patients.
  • Two-sample Mendelian randomization (MR) analysis used SNPs from GWAS datasets (deCODE and UK Biobank) to predict IL-6 and TNF-α signaling levels.
  • Outcome data included CRC-specific mortality from 16,964 CRC cases in the GECCO consortium.
  • Genetically predicted sIL6-RA showed a weak positive association with CRC-specific mortality.
  • Higher IL6ST levels were associated with increased mortality in stage 2/3 CRC patients.
  • No associations were found for TNF-α, sTNF-R1, or sTNF-R2 with CRC mortality.
  • Simulation indicated limited collider bias for TNF-α analyses.
  • Conclusions suggest IL-6 signaling may have a limited role in CRC progression, while TNF-related pathways appear less relevant for prognosis.