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Salicylic Acid and Risk of Colorectal Cancer: A Two-Sample Mendelian Randomization Study.

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Area of Science:

  • Genetics
  • Cancer Epidemiology
  • Pharmacogenomics

Background:

  • Salicylic acid (SA) is linked to reduced colorectal cancer (CRC) risk.
  • Aspirin, which metabolizes to SA, is a known chemopreventive agent.
  • Mendelian randomization (MR) can investigate causal relationships between SA and CRC.

Purpose of the Study:

  • To determine if genetically predicted salicylic acid (SA) levels influence colorectal cancer (CRC) risk.
  • To stratify the association between SA and CRC risk by aspirin use.

Main Methods:

  • Two-sample Mendelian randomization (MR) analysis using GWAS data for SA and CRC.
  • Selection of single nucleotide polymorphisms (SNPs) proxying SA through functional, pathway, and genome-wide significant approaches.
  • Replication and aspirin-use stratification using the DACHS study data.

Main Results:

  • No association was found between functional SNPs and SA levels.
  • Pathway and genome-wide significant SNPs showed no association between SA and CRC risk (ORs 1.03 and 1.08, respectively).
  • Results were consistent regardless of aspirin use stratification.

Conclusions:

  • Limited evidence suggests genetically predicted SA does not protect against CRC risk in the general population.
  • Stratification by aspirin use did not alter the observed lack of association.
  • Further research may be needed to clarify the role of SA in CRC chemoprevention.