Guo Xiaoxiao, Zhang Fengbo, Hao Gangyue
Department of Urology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.
Institute of Urology, Beijing Municipal Health Commission, Beijing, China.
Int J Urol. 2024 Dec;31(12):1356-1364. doi: 10.1111/iju.15565. Epub 2024 Sep 22.
Folic acid is a commonly used dietary supplement of trace element, but it may increase the risk of prostate cancer (PCa). The aim of this study was to investigate the causal relationship between PCa and folic acid supplementation, as well as dietary folate equivalents, using Mendelian randomization (MR) analysis.
The Genome-Wide Association Study (GWAS) data of folic acid supplementation and dietary folate equivalents were selected from UK Biobank. Meta-analysis of GWASs of PCa was obtained from PCa Association Group to Investigate Cancer-Associated Alterations in the Genome consortium. MR analysis was performed with inverse variance weighted (IVW) method, MR-Egger regression, simple mode, weighted median, and weighted mode analysis. Heterogeneity and horizontal pleiotropy tests and reverse MR analysis were conducted to assess the robustness and reliability of the causal inference.
Six single nucleotide polymorphisms (SNPs) associated with folic acid supplementation and five SNPs associated with dietary folate equivalents were identified as instrumental variables. Genetically predicted folic acid supplementation was associated with an increased risk of PCa (OR 1.200, p < 0.001, by IVW method), and there was no evidence of heterogeneity, horizontal pleiotropy, or significant reverse causality (all p > 0.05). In contrast, dietary folate equivalents showed no significant correlation with PCa (p > 0.05 for all five MR methods).
This study demonstrated an association between increased risk of PCa and folic acid supplementation, but not with dietary folate equivalents. These findings have implications for public health interventions and personalized preventive strategies for PCa.
叶酸是一种常用的微量元素膳食补充剂，但它可能会增加前列腺癌（PCa）的风险。本研究的目的是使用孟德尔随机化（MR）分析来研究PCa与叶酸补充剂以及膳食叶酸当量之间的因果关系。
从英国生物银行中选取叶酸补充剂和膳食叶酸当量的全基因组关联研究（GWAS）数据。前列腺癌GWAS的荟萃分析来自前列腺癌关联研究组以调查基因组中癌症相关改变联盟。采用逆方差加权（IVW）法、MR-Egger回归、简单模式、加权中位数和加权模式分析进行MR分析。进行异质性和水平多效性检验以及反向MR分析以评估因果推断的稳健性和可靠性。
六个与叶酸补充剂相关的单核苷酸多态性（SNP）和五个与膳食叶酸当量相关的SNP被确定为工具变量。基因预测的叶酸补充剂与PCa风险增加相关（通过IVW法，OR为1.200，p < 0.001），并且没有异质性、水平多效性或显著反向因果关系的证据（所有p > 0.05）。相比之下，膳食叶酸当量与PCa没有显著相关性（所有五种MR方法的p均> 0.05）。
本研究表明PCa风险增加与叶酸补充剂之间存在关联，但与膳食叶酸当量无关。这些发现对PCa的公共卫生干预和个性化预防策略具有启示意义。
