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Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Cancer Society Research Professor","id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Cancer Society Clinical Research Professor","award":["CRP-23-1014041"],"award-info":[{"award-number":["CRP-23-1014041"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Cancer Society Clinical Research Professor","award":["R00 CA207736"],"award-info":[{"award-number":["R00 CA207736"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R21 CA252962"],"award-info":[{"award-number":["R21 CA252962"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"name":"American Cancer Society Research Scholar","award":["RSG-17-190-01-NEC"],"award-info":[{"award-number":["RSG-17-190-01-NEC"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"crossref"}]},{"name":"American Cancer Society Mentored Research Scholar","award":["MRSG-17-220-01-NEC"],"award-info":[{"award-number":["MRSG-17-220-01-NEC"]}],"id":[{"id":"https:\/\/ror.org\/02e463172","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed prediagnostic metabolome-wide analyses with CRC risk.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a nested case-control study among women (Nurses\u2019 Health Study) and men (Health Professionals Follow-Up Study) who provided blood between 1989 and 1995. Over 22.9\u2009years, 684 (409 Nurses\u2019 Health Study, 275 Health Professionals Follow-Up Study) individuals developed CRC and were matched 1:1 to unaffected participants. Liquid chromatography-mass spectrometry identified 255 plasma metabolites after quality control. Cohort-specific and combined metabolite association analyses were performed using conditional logistic regression. Metabolite set enrichment analysis was used to identify differential abundance in metabolite classes. The R Weighted Correlation Network Analysis package provided modules of covarying metabolites, which were tested for CRC association.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Metabolite set enrichment analysis identified specific acylcarnitines associated with higher CRC risk and triacylglycerols with lower CRC risk among women and men. Further, phosphatidylcholines were associated with a higher risk of CRC among men. In an analysis restricted to CRC diagnosed 2 years after blood draw, myristoleic acid (odds ratio\u2009=\u20091.37 [95% CI\u2009=\u20091.15 to 1.62]; false discovery rate\u2009=\u20090.072) and C60:12 triacylglycerol (odds ratio\u2009=\u20090.75 [95% CI\u2009=\u20090.64 to 0.88]; false discovery rate\u2009=\u20090.072) were associated with CRC risk in women. Weighted correlation network analysis identified amino acids associated with CRC in men, fatty acid esters (carnitines) with distal CRC in men, and triradylcglycerols inversely associated with CRC in women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We identified prediagnostic CRC-associated metabolites with distinct sex-specific profiles. These results provide insight into CRC etiopathogenesis and have implications for risk prediction strategies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djae270","type":"journal-article","created":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T07:18:23Z","timestamp":1729840703000},"page":"517-528","source":"Crossref","is-referenced-by-count":11,"title":["Novel metabolomic predictors of incident colorectal cancer in men and women"],"prefix":"10.1093","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5424-4401","authenticated-orcid":false,"given":"Jonathan M","family":"Downie","sequence":"first","affiliation":[{"name":"Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital , Boston, MA,","place":["United States"]},{"name":"Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital , Boston, MA,","place":["United States"]},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit D","family":"Joshi","sequence":"additional","affiliation":[{"name":"Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital , Boston, MA,","place":["United States"]},{"name":"Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital , Boston, MA,","place":["United States"]},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connor M","family":"Geraghty","sequence":"additional","affiliation":[{"name":"Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital , Boston, MA,","place":["United States"]},{"name":"Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital , Boston, MA,","place":["United States"]},{"name":"Department of Epidemiology, Harvard T.H. Chan School of Public Health , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6296-2473","authenticated-orcid":false,"given":"Brendan J","family":"Guercio","sequence":"additional","affiliation":[{"name":"Department of Medicine, Brigham and Women\u2019s Hospital, Harvard Medical School , Boston, MA,","place":["United States"]},{"name":"Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8705-1163","authenticated-orcid":false,"given":"Oana A","family":"Zeleznik","sequence":"additional","affiliation":[{"name":"Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School , Boston, MA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1324-0316","authenticated-orcid":false,"given":"Mingyang","family":"Song","sequence":"additional","affiliation":[{"name":"Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital , Boston, MA,","place":["United States"]},{"name":"Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital , Boston, MA,","place":["United States"]},{"name":"Department of Epidemiology, Harvard T.H. 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Chan School of Public Health , Boston, MA,","place":["United States"]},{"name":"Department of Nutrition, Harvard T.H. 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