The causal association of colorectal cancer on the risk of membranous nephropathy: A Mendelian randomization study

Studies have suggested that colorectal cancer (CRC) and membranous nephropathy (MN) could be associated with each other. However, the existing conventional research methods fail to establish a conclusive relationship between the two conditions. The genome-wide association data for CRC and MN were obtained from previously published genome-wide association studies (GWAS). Inverse variance weighted (IVW), weighted median, weighted mode, and Mendelian randomization (MR)-Egger regression, were employed to analyze the data. Sensitivity analyses were conducted using the heterogeneity test, pleiotropic test, and leave-one-out test. Additionally, a reverse MR analysis was conducted to evaluate any potential reverse causal effects. The IVW analysis provided strong evidence supporting a causal link between CRC and MN (odds ratio (OR), 1.485; 95% confidence interval (CI), 1.131 - 1.951, p = 0.004). Similar findings were obtained from the weighted median analysis (OR, 1.515; 95% CI, 1.120 - 2.051, p = 0.007) and the weighted mode (OR, 1.572; 95% CI, 0.996 - 2.480, p = 0.084). The MR-Egger regression results indicated that the presence of horizontal pleiotropy was unlikely to bias the findings (intercept, -0.047; p = 0.611). MR-Egger regression did not show any causal association between CRC and MN (OR, 2.075; 95% CI, 0.584 - 7.373, p = 0.292). Reverse MR analysis suggested that MN is not a causative factor for CRC. Cochran's Q test, the funnel plot, and leave-one-out sensitivity analysis demonstrated the robustness of the MR study. Based on the genetic evidence obtained from this MR study, it can be concluded that CRC may serve as a risk factor for the development of MN. These findings will facilitate a future understanding of the mechanisms underlying MN.