{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T06:05:17Z","timestamp":1788156317790,"version":"build-2803163510"},"reference-count":65,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Carcinogenesis"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>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\u2010sample Mendelian randomization (MR) analysis. We used genetic instruments for 514 and 490 metabolites from two independent comprehensive genome\u2010wide association studies. These studies included 14,295 individuals of European ancestry from the INTERVAL\/EPIC\u2010Norfolk 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\u2010variance weighted method, supplemented by sensitivity analyses including MR\u2010Egger and MR\u2010PRESSO tests. Additionally, we conducted a phenome\u2010wide 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.<\/jats:p>","DOI":"10.1002\/mc.23929","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T10:30:26Z","timestamp":1747650626000},"page":"1318-1331","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Causal Relationship Between Blood Metabolites and Prostate Cancer Risk: A Two\u2010Sample Mendelian Randomization Study"],"prefix":"10.1002","volume":"64","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2244-2216","authenticated-orcid":false,"given":"Shuai","family":"Liu","sequence":"first","affiliation":[{"name":"Population Sciences in the Pacific Program, Cancer Epidemiology Division University of Hawai\u02bbi Cancer Center, University of Hawai\u02bbi at M\u0101noa Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Quantitative Health Sciences, John A. Burns School of Medicine University of Hawai\u02bbi at M\u0101noa Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huizhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Population Sciences in the Pacific Program, Cancer Epidemiology Division University of Hawai\u02bbi Cancer Center, University of Hawai\u02bbi at M\u0101noa Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9358-1582","authenticated-orcid":false,"given":"Hua","family":"Zhong","sequence":"additional","affiliation":[{"name":"Population Sciences in the Pacific Program, Cancer Epidemiology Division University of Hawai\u02bbi Cancer Center, University of Hawai\u02bbi at M\u0101noa Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoi Tung Hilton","family":"Wong","sequence":"additional","affiliation":[{"name":"Population Sciences in the Pacific Program, Cancer Epidemiology Division University of Hawai\u02bbi Cancer Center, University of Hawai\u02bbi at M\u0101noa Honolulu Hawaii USA"},{"name":"Biochemistry Program, Department of Chemistry, Colleges of Arts and Sciences University of Hawai\u02bbi at M\u0101noa Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9364-8572","authenticated-orcid":false,"given":"Liang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Tumor Microenvironment and Metastasis Moffitt Cancer Center Tampa Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9938-3627","authenticated-orcid":false,"given":"Lang","family":"Wu","sequence":"additional","affiliation":[{"name":"Population Sciences in the Pacific Program, Cancer Epidemiology Division University of Hawai\u02bbi Cancer Center, University of Hawai\u02bbi at M\u0101noa Honolulu Hawaii USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,5,19]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27175730"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbcan.2024.189080"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines12010079"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddad139"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2023.0065"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23828"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24774"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-024-05190-y"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.2147\/PGPM.S319308"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.33808"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-17673-9"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-3997"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-18-3536"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.3710"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21670"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-023-02400-9"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.21766"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737159.2019.1656530"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2024.1443330"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCO.0000000000000276"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.16775"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12060488"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2017.00131"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo9030048"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyx028"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw127"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.14309\/ajg.0000000000003048"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2024.105233"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2023.101391"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12082961"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/trc2.12148"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-20-0651"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/1055-9965.EPI-18-0079"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-022-08442-7"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-022-02046-0"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-022-01270-1"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01534-4"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.34771"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2023.104798"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000559"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10654-017-0255-x"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0099-7"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.6022"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkq603"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-018-0175-2"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkae253"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-018-0184-y"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btaa731"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1677\/ERC-10-0032"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-30590-3"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.02.009"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/pcan.2013.13"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/6158436"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1002\/nbm.1738"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.28303"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0045(20001201)45:4<350::AID-PROS10>3.0.CO;2-U"},{"key":"e_1_2_11_60_1","volume-title":"Molecular Imaging and Contrast Agent Database (MICAD)","author":"Leung K.","year":"2004"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.4103\/aja2021104"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-021-03990-9"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a030486"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2022.07.008"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2021.107932"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/mc.23676"}],"container-title":["Molecular Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mc.23929","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,25]],"date-time":"2025-07-25T12:46:51Z","timestamp":1753447611000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mc.23929"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,19]]},"references-count":65,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2025,8]]}},"alternative-id":["10.1002\/mc.23929"],"URL":"https:\/\/doi.org\/10.1002\/mc.23929","archive":["Portico"],"relation":{},"ISSN":["0899-1987","1098-2744"],"issn-type":[{"value":"0899-1987","type":"print"},{"value":"1098-2744","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,5,19]]},"assertion":[{"value":"2025-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-27","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}