Absence of genetic association between insulin-like growth factors and esophageal cancer

This study aimed to explore the causal relationship between concentrations of various insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) and esophageal cancer (ESC), addressing the gap in understanding the genetic link between IGF1 and ESC. A two-sample Mendelian randomization (MR) analysis was conducted using single nucleotide polymorphisms linked to IGFs/IGFBPs and ESC from the IEU Open GWAS Project. This analysis included ESC GWAS data from 1996 individuals of European descent and genetic variant data from 3310 individuals of European ancestry. Various methods, such as inverse variance weighting, weighted median, weighted mode, and MR-Egger regression, were applied for analysis, with sensitivity assessments including MR-PRESSO, Cochran Q, and leave-one-out analysis to ensure the robustness of results and detect biases. The genetic predictions indicated no significant association between IGFs/IGFBPs and ESC. When ESC was the outcome measure, the odds ratios with 95% confidence intervals were as follows: IGF1 = 1.00 (0.89-1.12, P = .936), IGF1R = 1.07 (0.90-1.27, P = .453), IGFBP3 = 1.00 (0.79-1.26, P = .975), and IGFBPL1 = 0.91 (0.75-1.12, P = .372). MR-Egger regression confirmed the absence of horizontal pleiotropy, and no outliers were identified by MR-PRESSO. Leave-one-out analysis supported the stability of the results. The study did not find a causal connection between IGFs/IGFBPs and ESC. These results suggest the need for further validation and potentially highlight the complex interplay of factors involved in the development of ESC.