Exploring causal correlations between inflammatory cytokines and colorectal cancer: A 2-sample Mendelian randomization study

Colorectal cancer (CRC) is a significant global public health concern. Several observational studies have examined the association between inflammatory cytokines and the risk of colorectal cancer, but the findings have been inconsistent. In this study, we employed a 2-sample Mendelian randomization (MR) analysis, primarily using the inverse variance weighted approach, to investigate the causal relationship between inflammatory cytokines and CRC. The forward MR analysis revealed a positive association between higher levels of interleukin (IL)-16 (OR: 1.37, P = .002), vascular endothelial growth factor (OR: 1.44, P = .001), and MIG (OR: 1.23, P = .040) with an increased risk of rectal cancer. Conversely, higher levels of macrophage colony-stimulating factor (OR: 0.80, P = .010) may potentially decrease the risk of colon cancer. In the reverse MR analysis, it was found that rectal cancer is linked to higher levels of IL-1b (OR: 0.93, P = .022), IL-1ra (OR: 0.90, P = .001), IL-5 (OR: 0.93, P = .022), IL-9 (OR: 0.93, P = .017), and TNF-a (OR: 0.91, P = .003). Additionally, colon cancer is associated with elevated levels of FGF-Basic (OR: 1.10, P = .028). Consistent results were also found in MR-Egger, weighted median, and weighted mode analysis. Our study presents novel evidence supporting the causal relationship between inflammatory cytokines and CRC.