Abstract:

Objective To explore the causal association between insulin-like growth factor-1（IGF-1） and colorectal cancer（CRC） based on two sample Mendelian randomization（MR） analysis. Methods A bidirectional two sample MR analysis was conducted based on publicly aggregated data from the IEU OpenGWAS project. The inverse variance weighted（IVW） method was used as the main analysis model to assess the causal relationship between IGF-1 and CRC. Additional analyses were performed using weighted median （WM）， MR-Egger regression， weighted mode estimator （WME）， and simple mode （SM） methods. Sensitivity analysis was performed to assess the robustness of the results. Results A total of 386 single nucleotide polymorphisms（SNPs）were selected as instrumental variables （IVs） with IGF-1 as the exposure factor. The MR analysis results revealed a positive causal association between IGF-1 and the risk of CRC ［odds ratio （OR）=1.178， 95% confidence interval （CI）： 1.092-1.272）］（P<0.001）， and the association remained significant after adjusting for height ［OR（95%CI）=1.214（1.111， 1.327）］（P<0.001）. Cochran’s Q-test showed heterogeneity among the IVs（P<0.05）， while the horizontal pleiotropy of IV was not detected by the MR-Egger regression（P>0.05）. The leave-one-out analysis showed that the MR results were robust. Reverse MR analysis indicated no reverse causal relationship between IGF-1 and CRC ［OR（95%CI）：1.017（0.997， 1.037）］（P=0.103）. Conclusion There is a causal relationship between IGF-1 level and CRC， and elevated IGF-1 level could be a risk factor for CRC.

Key words: Insulin-like growth factor-1, Colorectal cancer, Mendelian randomization, Height, Single nucleotide polymorphism