ABSTRACT
Objective To investigate the association between primary sclerosing cholangitis (PSC) and colorectal cancer (CRC) by using two-sample Mendelian randomization (TSMR). Methods The single nucleotide polymorphism (SNP) data associated with PSC and CRC were obtained from Finland Biobank and UK Biobank, respectively. A secondary data analysis was performed for all pooled data based on genome-wide association studies to select the genetic loci closely associated with PSC as instrumental variables, and TSMR was conducted by seven methods, i.e., Egger regression in Mendelian randomization, weighted median, inverse variance weighted (IVW) random effects model, maximum likelihood, linear weighted median, IVW radial method, and IVW fixed effects model. Odds ratio (OR) value was used to evaluate the causal relationship between PSC and the risk of CRC. Results There was a positive causal relationship between gene predicted PSC and CRC, and with the IVW fixed effects model as an example, genetically determined patients with PSC could increase the risk of CRC ( OR =1.002 243, 95% confidence interval: 1.001 319-1.003 167). TSMR results showed no heterogeneity ( P =0.87) or horizontal pleiotropy ( P =0.95). The three instrumental variables selected for PSC were strong instrumental variables ( F =11.86). Conclusion TSMR shows the genetic evidence for the association between PSC and the risk of CRC. Regardless of the presence or absence of inflammatory bowel disease, active enteroscopy screening among patients with PSC may help with the early identification and timely intervention of CRC.