Vascular endothelial growth factor and colorectal cancer risk: A two sample mendelian randomization analysis

Numerous clinical studies have found that high expression of Vascular Endothelial Growth Factor (VEGF) is closely associated with poor prognosis in Colorectal Cancer (CRC), including high tumor recurrence rates and short survival periods. However, observational studies are prone to confounding factors or reverse causality. In this study, we used Single Nucleotide Polymorphisms (SNPs) as instrumental variables and employed the Mendelian randomization method to investigate the causal relationship between genetically determined elevated VEGF levels and CRC risk.

Methods: Data for CRC were obtained from the Finnish database (R10), which included 6,847 CRC cases and 314,193 controls. VEGF data were sourced from the IEU database, comprising 7,118 samples and 9,784,803 SNPs. As instrumental variables, we selected SNPs previously associated with VEGF concentrations. Logistic regression models adjusted for age, sex, principal components, and genotyping batch were used to estimate the associations between SNPs and CRC. The causal effect of VEGF on CRC risk was estimated using the Inverse Variance Weighted (IVW) method.

Results: A total of three SNPs met the criteria as instrumental variables. The IVW method revealed that VEGF is a risk factor for CRC (beta = 0.08, se = 0.03, p = 0.01). The trends obtained using MR Egger and Weighted Median methods were consistent with those from the IVW method.

Conclusion: We found that genetically elevated VEGF concentrations are associated with increased CRC risk in individuals of European descent. Our results further suggest that elevated circulating VEGF levels are a causal factor in the development of CRC.

Dr. Xia is a specialist in gastrointestinal surgery, holding a M.D. from Kunming Medical University. He is currently affiliated with the Second Affiliated Hospital of Kunming Medical University. Dr. Xia has extensive experience in the diagnosis and treatment of gastrointestinal diseases and has published several papers in this field. He is actively involved in clinical research and is committed to improving patient outcomes in gastrointestinal surgery.