The causal effect of serum micronutrients on malignant kidney neoplasm in European descent

Abstract

Purpose: Observational studies have revealed that serum minerals and vitamins are associated with cancer. However, the causal relationships between serum minerals and vitamins and renal malignancies remain unclear. Methods: Mendelian randomization (MR) was used for causal estimation. Single nucleotide polymorphisms (SNPs) for serum minerals and vitamins were obtained from published genome-wide association studies (GWAS). GWAS for malignant kidney neoplasm was obtained from the FinnGen consortium. Methods of inverse variance weighted (IVW), MR-Egger, and weighted median were carried out for causal inference. F-statistic was calculated to ensure a robust instrumental variable. Cochran’s Q statistics was applied to calculate heterogeneity. MR-Egger regression, MR-pleiotropy residual sum and outlier methods (MR-PRESSO) methods were used to perform pleiotropy analysis. Meanwhile, confounding factors were considered to determine whether causal inference would be biased. Results: Eight different micronutrients were included (zinc, iron, magnesium, calcium, copper, selenium, phosphate, and vitamin B12). After MR analysis, we found a protective effect of serum zinc against malignant kidney neoplasm (IVW: odds ratios (ORs), 0.86; 95% confidence interval (95% CI), 0.78–0.94; p, 0.0016; MR-Egger: OR, 0.80; 95% CI, 0.64–0.97; p, 0.052; weighted median: OR, 0.85; 95% CI, 0.75–0.96; p, 0.011). Causal relationships between other micronutrients and malignant kidney neoplasm were not obtained. No heterogeneity and pleiotropy were detected, while causality was not biased by confounding factors. Conclusion: We considered that serum zinc exerted a protective effect against malignant kidney neoplasm. In clinical practice, for people with high malignant kidney neoplasm risk, an oral zinc supplementation might play a role in a potential therapeutic target.