Causal relationship between renal function and risk of esophageal cancer: insights from Mendelian randomization.

Background: Previous studies have indicated a potential correlation between renal function and risk of cancer. However, establishing a causal relationship is challenging. To address this, we employed Mendelian randomization (MR), a novel method that utilizes genotype data to simulate randomized trial groups, to investigate whether there is a causal correlation between renal function and the esophageal cancer (EC) risk. Methods: MR analysis was conducted with the individual-level data on EC from the UK Biobank published dataset. Genetic instruments were derived from single nucleotide polymorphisms (SNPs) extracted from publicly available genome-wide association studies. Furthermore, leave-one-out sensitivity analysis was performed to assess the impact of individual SNPs. Results: In our MR analysis, we examined 39,475,182 SNPs associated with various renal functional indexes from public databases. Based on the primary causal effects model using MR analyses with the inverse variance weighted method, the genetically predicted cystatin C [odds ratio (OR) =1.0005, 95% confidence interval (CI): 1.0000-1.0009; P=0.05] and creatinine (OR =1.0016, 95% CI: 1.0002-1.0031; P=0.02) demonstrated a significant association with higher risk of EC. However, we found no evidence of an association between urinary albumin and glomerular filtration rate with the risk of EC. Conclusions: Our research provides strong evidence for the association of decreased renal function to a potential risk of EC. However, it is crucial to recognize the necessity for additional large-scale prospective studies to validate this discovery and establish a comprehensive understanding of the causal relationships between renal function and EC. Keywords: Esophageal cancer (EC); renal function; Mendelian randomization (MR); causal association.