{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T16:39:14Z","timestamp":1766507954460,"version":"3.48.0"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"1203","license":[{"start":{"date-parts":[[2025,7,28]],"date-time":"2025-07-28T00:00:00Z","timestamp":1753660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,12,23]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>An association between the one-carbon metabolism molecules, such as vitamin B6 (VB6), vitamin B12 (VB12), folate and homocysteine (Hcy), and the incidence of various cancers risk has been reported in observational studies, but the causal relationship between one-carbon metabolism molecules and various cancers risk remains unclear. Our aim was to assess the causal effect of one-carbon metabolism molecules on various cancers risk using a two-sample Mendelian randomization (MR) approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed two-sample MR to analyze associations between four one-carbon metabolism molecules and seven cancers in Europeans. Methods included IVW, weighted median, MR-Egger, MR-PRESSO, and outlier tests.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Hcy: Suggestive causal association with reduced GC risk (OR\u2009=\u20090.5427; P\u2009=\u2009.0217) and increased KC risk (OR\u2009=\u20091.3744; P\u2009=\u2009.0465). High Hcy levels linked to higher PCA (OR\u2009=\u20091.1038; P\u2009=\u2009.0496) and KC risk (OR\u2009=\u20091.5444; P\u2009=\u2009.0430), but lower GC risk (OR\u2009=\u20090.6487; P\u2009=\u2009.0499).<\/jats:p>\n                    <jats:p>Folate: Higher levels associated with increased CRC risk (OR\u2009=\u20091.2945; P\u2009=\u2009.0346) and reduced PCA risk (OR\u2009=\u20090.8330; P\u2009=\u2009.0486).<\/jats:p>\n                    <jats:p>VB12: Suggestive causal association with reduced BC (OR\u2009=\u20090.7421; P\u2009=\u2009.0203) and GC risk (OR\u2009=\u20090.4812; P\u2009=\u2009.0267). The causal associations of the above combinations were robust through the test of heterogeneity and pleiotropy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The large MR analysis indicated that one-carbon metabolism molecules may be causally associated with various cancers risk.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/postmj\/qgaf114","type":"journal-article","created":{"date-parts":[[2025,7,17]],"date-time":"2025-07-17T10:08:29Z","timestamp":1752746909000},"page":"25-31","source":"Crossref","is-referenced-by-count":0,"title":["Causal effects of one-carbon metabolism molecules on cancers risk: a Mendelian randomization study"],"prefix":"10.1093","volume":"102","author":[{"given":"Xiao","family":"Li","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders , No. 20, Jinyu Avenue, Liangjiang New Area,Chongqing, 400015 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Man","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders , No. 20, Jinyu Avenue, Liangjiang New Area,Chongqing, 400015 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simeng","family":"Gao","sequence":"additional","affiliation":[{"name":"Research Center of Cancer Diagnosis and Therapy, Department of Oncology, The First Affiliated Hospital of Jinan University , No. 613, Huangpu Avenue West, Guangzhou, Guangdong, 510700 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingru","family":"Han","sequence":"additional","affiliation":[{"name":"Research Center of Cancer Diagnosis and Therapy, Department of Oncology, The First Affiliated Hospital of Jinan University , No. 613, Huangpu Avenue West, Guangzhou, Guangdong, 510700 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ping","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Children\u2019s Hospital of Chongqing Medical University, National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders , No. 20, Jinyu Avenue, Liangjiang New Area,Chongqing, 400015 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,7,28]]},"reference":[{"key":"2025122309515532800_ref1","doi-asserted-by":"publisher","first-page":"1499","DOI":"10.1038\/bjc.2017.118","article-title":"One-carbon metabolism in cancer","volume":"116","author":"Newman","year":"2017","journal-title":"Br J Cancer"},{"key":"2025122309515532800_ref2","doi-asserted-by":"publisher","first-page":"101850","DOI":"10.1016\/j.redox.2020.101850","article-title":"The toxic side of one-carbon metabolism and epigenetics","volume":"40","author":"Morellato","year":"2021","journal-title":"Redox Biol"},{"key":"2025122309515532800_ref3","doi-asserted-by":"publisher","first-page":"e1426","DOI":"10.1002\/wsbm.1426","article-title":"Cell cycle regulation of folate-mediated one-carbon metabolism","volume":"10","author":"Lan","year":"2018","journal-title":"Wiley Interdiscip Rev Syst Biol Med"},{"key":"2025122309515532800_ref4","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1002\/jimd.12009","article-title":"Vitamin B12 , folate, and the methionine remethylation cycle-biochemistry, pathways, and regulation","volume":"42","author":"Froese","year":"2019","journal-title":"J Inherit Metab Dis"},{"key":"2025122309515532800_ref5","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1016\/j.jnutbio.2012.03.003","article-title":"Nutrition and epigenetics: an interplay of dietary methyl donors, one-carbon metabolism and DNA methylation","volume":"23","author":"Anderson","year":"2012","journal-title":"J Nutr Biochem"},{"key":"2025122309515532800_ref6","doi-asserted-by":"publisher","DOI":"10.3389\/fpubh.2023.1177707","article-title":"Editorial: epidemiology and molecular epidemiology of childhood and adolescent cancers","volume":"11","author":"Spector","year":"2023","journal-title":"Front Public Health"},{"key":"2025122309515532800_ref7","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1146\/annurev-pathmechdis-012418-012818","article-title":"Insights into pathogenic interactions among environment, host, and tumor at the crossroads of molecular pathology and epidemiology","volume":"14","author":"Ogino","year":"2019","journal-title":"Annu Rev Pathol"},{"key":"2025122309515532800_ref8","doi-asserted-by":"publisher","first-page":"1632","DOI":"10.1158\/1055-9965.EPI-10-0180","article-title":"Circulating folate, vitamin B12, homocysteine, vitamin B12 transport proteins, and risk of prostate cancer: a case-control study, systematic review, and meta-analysis","volume":"19","author":"Collin","year":"2010","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2025122309515532800_ref9","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1002\/ijc.20646","article-title":"Plasma folate, vitamin B12, and homocysteine and prostate cancer risk: a prospective study","volume":"113","author":"Hultdin","year":"2005","journal-title":"Int J Cancer"},{"key":"2025122309515532800_ref10","doi-asserted-by":"publisher","first-page":"4192","DOI":"10.26355\/eurrev_201905_17922","article-title":"Correlations of serum homocysteine, VEGF and gastrin 17 with gastric cancer and precancerous lesions","volume":"23","author":"Zhao","year":"2019","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"2025122309515532800_ref11","doi-asserted-by":"publisher","first-page":"e0214462","DOI":"10.1371\/journal.pone.0214462","article-title":"Folate\/homocysteine metabolism and lung cancer risk among smokers","volume":"14","author":"Stanis\u0142awska-Sachadyn","year":"2019","journal-title":"PLoS One"},{"key":"2025122309515532800_ref12","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1080\/01635581.2015.989375","article-title":"Plasma folate, vitamin B12, and homocysteine and cancers of the esophagus, stomach, and liver in a Chinese population","volume":"67","author":"Chang","year":"2015","journal-title":"Nutr Cancer"},{"key":"2025122309515532800_ref13","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1080\/13510002.2016.1183348","article-title":"Homocysteine pre-treatment increases redox capacity in both endothelial and tumor cells","volume":"22","author":"Chang","year":"2017","journal-title":"Redox Rep"},{"key":"2025122309515532800_ref14","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17101733","article-title":"The molecular and cellular effect of homocysteine metabolism imbalance on human health","volume":"17","author":"\u0160kovierov\u00e1","journal-title":"Int J Mol Sci"},{"key":"2025122309515532800_ref15","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.3945\/jn.115.225433","article-title":"Plasma riboflavin and vitamin B-6, but not homocysteine, folate, or vitamin B-12, are inversely associated with breast cancer risk in the European prospective investigation into cancer and nutrition-Varese cohort","volume":"146","author":"Agnoli","year":"2016","journal-title":"J Nutr"},{"key":"2025122309515532800_ref16","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1186\/s13059-016-1018-9","article-title":"Mendelian randomization in (epi) genetic epidemiology: an effective tool to be handled with care","volume":"17","author":"Latvala","year":"2016","journal-title":"Genome Biol"},{"key":"2025122309515532800_ref17","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1002\/path.5421","article-title":"The use of mendelian randomisation to identify causal cancer risk factors: promise and limitations","volume":"250","author":"Gala","year":"2020","journal-title":"J Pathol"},{"key":"2025122309515532800_ref18","doi-asserted-by":"publisher","first-page":"668","DOI":"10.3945\/ajcn.112.044545","article-title":"Common genetic loci influencing plasma homocysteine concentrations and their effect on risk of coronary artery disease","volume":"98","author":"van Meurs","year":"2013","journal-title":"Am J Clin Nutr"},{"key":"2025122309515532800_ref19","doi-asserted-by":"publisher","first-page":"1287","DOI":"10.1038\/mp.2016.252","article-title":"Cannabis use and risk of schizophrenia: a mendelian randomization study","volume":"23","author":"Vaucher","year":"2018","journal-title":"Mol Psychiatry"},{"key":"2025122309515532800_ref20","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1038\/s41588-020-0609-2","article-title":"Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses","volume":"52","author":"Zhang","year":"2020","journal-title":"Nat Genet"},{"key":"2025122309515532800_ref21","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/ng.3892","article-title":"Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes","volume":"49","author":"McKay","year":"2017","journal-title":"Nat Genet"},{"key":"2025122309515532800_ref22","doi-asserted-by":"publisher","first-page":"928","DOI":"10.1038\/s41588-018-0142-8","article-title":"Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci","volume":"50","author":"Schumacher","year":"2018","journal-title":"Nat Genet"},{"key":"2025122309515532800_ref23","doi-asserted-by":"publisher","first-page":"4423","DOI":"10.1038\/s41467-020-18246-6","article-title":"Pan-cancer study detects genetic risk variants and shared genetic basis in two large cohorts","volume":"11","author":"Rashkin","year":"2020","journal-title":"Nat Commun"},{"key":"2025122309515532800_ref24","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","article-title":"Mendelian randomization with invalid instruments: effect estimation and bias detection through egger regression","volume":"44","author":"Bowden","year":"2015","journal-title":"Int J Epidemiol"},{"key":"2025122309515532800_ref25","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","article-title":"Interpreting findings from mendelian randomization using the MR-egger method","volume":"32","author":"Burgess","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"2025122309515532800_ref26","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1002\/gepi.22207","article-title":"Implementing MR-PRESSO and GCTA-GSMR for pleiotropy assessment in mendelian randomization studies from a practitioner's perspective","volume":"43","author":"Ong","year":"2019","journal-title":"Genet Epidemiol"},{"key":"2025122309515532800_ref27","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/s0006-3223(03)00566-3","article-title":"Depression and cancer: mechanisms and disease progression","volume":"54","author":"Spiegel","year":"2003","journal-title":"Biol Psychiatry"},{"key":"2025122309515532800_ref28","doi-asserted-by":"publisher","first-page":"487","DOI":"10.1158\/1055-9965.EPI-19-0724","article-title":"Genetic Association of Plasma Homocysteine Levels with gastric cancer risk: a two-sample mendelian randomization study","volume":"29","author":"Wang","year":"2020","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2025122309515532800_ref29","doi-asserted-by":"publisher","first-page":"2526","DOI":"10.1158\/1078-0432.CCR-06-2293","article-title":"Polymorphisms of MTHFD, plasma homocysteine levels, and risk of gastric cancer in a high-risk Chinese population","volume":"13","author":"Wang","year":"2007","journal-title":"Clin Cancer Res"},{"key":"2025122309515532800_ref30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s12276-019-0216-4","article-title":"Disturbed homocysteine metabolism is associated with cancer","volume":"51","author":"Hasan","year":"2019","journal-title":"Exp Mol Med"},{"key":"2025122309515532800_ref31","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20133140","article-title":"Dysregulation of epigenetic mechanisms of gene expression in the pathologies of Hyperhomocysteinemia","volume":"20","author":"Per\u0142a-Kaj\u00e1n","journal-title":"Int J Mol Sci"},{"key":"2025122309515532800_ref32","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1002\/ijc.21712","article-title":"The role of folate receptor alpha in cancer development, progression and treatment: cause, consequence or innocent bystander?","volume":"119","author":"Kelemen","year":"2006","journal-title":"Int J Cancer"},{"key":"2025122309515532800_ref33","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/pcan.2014.16","article-title":"Folate intake and the risk of prostate cancer: a systematic review and meta-analysis","volume":"17","author":"Tio","year":"2014","journal-title":"Prostate Cancer Prostatic Dis"},{"key":"2025122309515532800_ref34","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1021\/acs.bioconjchem.0c00625","article-title":"Folic acid-functionalized nanomedicine: folic acid conjugated copolymer and folate receptor interactions disrupt receptor functionality resulting in dual therapeutic anti-cancer potential in breast and prostate cancer","volume":"32","author":"DeCarlo","year":"2021","journal-title":"Bioconjug Chem"},{"key":"2025122309515532800_ref35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1093\/jnci\/djw230","article-title":"Vitamin B6 and cancer risk: a Field synopsis and meta-analysis","volume":"109","author":"Mocellin","year":"2017","journal-title":"J Natl Cancer Inst"}],"container-title":["Postgraduate Medical Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pmj\/article-pdf\/102\/1203\/25\/63865277\/qgaf114.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pmj\/article-pdf\/102\/1203\/25\/63865277\/qgaf114.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,23]],"date-time":"2025-12-23T14:52:03Z","timestamp":1766501523000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pmj\/article\/102\/1203\/25\/8215420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,28]]},"references-count":35,"journal-issue":{"issue":"1203","published-online":{"date-parts":[[2025,7,28]]},"published-print":{"date-parts":[[2025,12,23]]}},"URL":"https:\/\/doi.org\/10.1093\/postmj\/qgaf114","relation":{},"ISSN":["0032-5473","1469-0756"],"issn-type":[{"type":"print","value":"0032-5473"},{"type":"electronic","value":"1469-0756"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,7,28]]}}}