Genetic susceptibility association between viral infection and colorectal cancer risk: a two-sample Mendelian randomization analysis

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BackgroundThe genetic susceptibility association between viral infection and the risk of colorectal cancer (CRC) has not been established.MethodsWe conducted two-sample Mendelian randomization (MR) analysis using genome-wide association study (GWAS) data. In addition to traditional MR methods, we employed several other approaches, including cML, ConMix, MR-RAPS, and dIVW, to comprehensively assess causal effects. Sensitivity analyses were also performed to ensure the robustness of the results.ResultsAfter sensitivity analysis, presence of SNPs linked to increased susceptibility to cold sores infection was found to decrease the risk of CRC (OR: 0.73, 95% CI: 0.57–0.93, P = 0.01). In subgroup analysis, presence of SNPs linked to increased susceptibility to viral hepatitis (OR: 0.89, 95% CI: 0.81–0.98, P = 0.02) and infectious mononucleosis (OR: 0.91, 95% CI: 0.84–0.98, P = 0.02) were associated with a decreased risk of colon cancer, while measles virus (OR: 1.41, 95% CI: 1.07–1.85, P = 0.01) was associated with an increased risk of colon cancer. Presence of SNPs linked to increased susceptibility to herpes zoster (OR: 1.26, 95% CI: 1.05–1.52, P = 0.01) was associated with an increased risk of rectal cancer, while infectious mononucleosis (OR: 0.809, 95% CI: 0.80–0.98, P = 0.02) was associated with a decreased risk.ConclusionThe study provides the first evidence of the genetic susceptibility associations between different viral infections and CRC, enhancing our understanding of the etiology of CRC.