Qiao Pengfei, Tian Zhentao
The Department of Urology Surgery, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China.
National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China.
Front Oncol. 2023 Aug 16;13:1191825. doi: 10.3389/fonc.2023.1191825. eCollection 2023.
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.
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.
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; , 0.0016; MR-Egger: OR, 0.80; 95% CI, 0.64-0.97; , 0.052; weighted median: OR, 0.85; 95% CI, 0.75-0.96; , 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.
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.
观察性研究表明血清矿物质和维生素与癌症有关。然而，血清矿物质和维生素与肾恶性肿瘤之间的因果关系仍不清楚。
采用孟德尔随机化（MR）进行因果估计。血清矿物质和维生素的单核苷酸多态性（SNP）来自已发表的全基因组关联研究（GWAS）。恶性肾肿瘤的GWAS来自芬兰基因组联盟。采用逆方差加权（IVW）、MR-Egger和加权中位数方法进行因果推断。计算F统计量以确保工具变量的稳健性。应用 Cochr an's Q统计量计算异质性。采用MR-Egger回归、MR-多效性残差和异常值方法（MR-PRESSO）进行多效性分析。同时，考虑混杂因素以确定因果推断是否会产生偏差。
纳入了八种不同的微量营养素（锌、铁、镁、钙、铜、硒、磷酸盐和维生素B12）。经过MR分析，我们发现血清锌对恶性肾肿瘤有保护作用（IVW：比值比（OR），0.86；95%置信区间（95%CI），0.78-0.94；P，0.0016；MR-Egger：OR，0.80；95%CI，0.64-0.97；P，0.052；加权中位数：OR，0.85；95%CI，0.75-0.96；P，0.011）。未发现其他微量营养素与恶性肾肿瘤之间的因果关系。未检测到异质性和多效性，而因果关系不受混杂因素的影响。
我们认为血清锌对恶性肾肿瘤具有保护作用。在临床实践中，对于肾恶性肿瘤风险较高的人群，口服补锌可能在潜在治疗靶点中发挥作用。
