Liu Shuai, Zhu Jingjing, Zhang Huizhen, Zhong Hua, Wong Hoi Tung Hilton, Wang Liang, Wu Lang
Population Sciences in the Pacific Program, Cancer Epidemiology Division, University of Hawai'i Cancer Center, University of Hawai'i at Mānoa, Honolulu, Hawaii, USA.
Department of Quantitative Health Sciences, John A. Burns School of Medicine, University of Hawai'i at Mānoa, Honolulu, Hawaii, USA.
Mol Carcinog. 2025 Aug;64(8):1316-1329. doi: 10.1002/mc.23929. Epub 2025 May 19.
Recent research has increasingly suggested an association between changes in specific blood metabolites and prostate cancer (PCa) development. However, it remains unclear whether these observed associations represent a causal relationship. To reveal the potential causal associations between blood metabolites and PCa risk, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis. We used genetic instruments for 514 and 490 metabolites from two independent comprehensive genome-wide association studies. These studies included 14,295 individuals of European ancestry from the INTERVAL/EPIC-Norfolk cohorts and 8299 individuals of European ancestry from the Canadian Longitudinal Study on Aging cohort. Summary statistics of PCa risk involving 122,188 cases and 604,640 controls of European ancestry individuals were analyzed. The associations between metabolites and PCa risk were evaluated using the inverse-variance weighted method, supplemented by sensitivity analyses including MR-Egger and MR-PRESSO tests. Additionally, we conducted a phenome-wide MR analysis to assess the potential side effects of targeting the identified metabolites for PCa intervention. Our analysis revealed 107 unique blood metabolites significantly associated with PCa risk, with 43 of these associations consistently replicated using instruments from two independent data sets. This study provides novel insights into the potential role of specific metabolites in the etiology of PCa, which warrants further investigations.
近期研究越来越多地表明特定血液代谢物的变化与前列腺癌（PCa）的发生之间存在关联。然而，这些观察到的关联是否代表因果关系仍不清楚。为了揭示血液代谢物与PCa风险之间潜在的因果关联，我们进行了一项全面的两样本孟德尔随机化（MR）分析。我们使用了来自两项独立的全基因组关联研究的514种和490种代谢物的基因工具。这些研究包括来自INTERVAL/EPIC-Norfolk队列的14295名欧洲血统个体和来自加拿大衰老纵向研究队列的8299名欧洲血统个体。分析了涉及122188例病例和604640例欧洲血统个体对照的PCa风险汇总统计数据。使用逆方差加权法评估代谢物与PCa风险之间的关联，并辅以包括MR-Egger和MR-PRESSO检验在内的敏感性分析。此外，我们进行了全表型组MR分析，以评估针对已识别的代谢物进行PCa干预的潜在副作用。我们的分析揭示了107种与PCa风险显著相关的独特血液代谢物，其中43种关联使用来自两个独立数据集的工具得到了一致重复。这项研究为特定代谢物在PCa病因学中的潜在作用提供了新的见解，值得进一步研究。
