Jonathan M Downie, Amit D Joshi, Connor M Geraghty, Brendan J Guercio, Oana A Zeleznik, Mingyang Song, Alaina M Bever, David A Drew, Fred K Tabung, Xuehong Zhang, Lina Jin, A Heather Eliassen, Walter C Willett, Kana Wu, Peter Kraft, Rulla Tamimi, Clary Clish, Charles S Fuchs, Edward Giovannucci, Jeffrey A Meyerhardt, Andrew T Chan
{"title":"Novel metabolomic predictors of incident colorectal cancer in men and women.","authors":"Jonathan M Downie, Amit D Joshi, Connor M Geraghty, Brendan J Guercio, Oana A Zeleznik, Mingyang Song, Alaina M Bever, David A Drew, Fred K Tabung, Xuehong Zhang, Lina Jin, A Heather Eliassen, Walter C Willett, Kana Wu, Peter Kraft, Rulla Tamimi, Clary Clish, Charles S Fuchs, Edward Giovannucci, Jeffrey A Meyerhardt, Andrew T Chan","doi":"10.1093/jnci/djae270","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed pre-diagnostic metabolome-wide analyses with CRC risk.</p><p><strong>Methods: </strong>We conducted a nested case-control study among women (Nurses' Health Study (NHS)) and men (Health Professionals Follow-up Study (HPFS)) who provided blood between 1989 and 1995. Over 22.9 years, 684 (409 NHS, 275 HPFS) incident CRC cases occurred and were matched 1:1 to controls. Liquid chromatography-mass spectrometry (LC-MS) identified 255 plasma metabolites after quality control. Cohort-specific and combined metabolite association analyses were performed using conditional logistic regression. Metabolite set enrichment analysis (MSEA) was used to identify differential abundance in metabolite classes. Weighted Correlation Network Analysis (WGCNA) provided modules of covarying metabolites, which were tested for CRC association.</p><p><strong>Results: </strong>MSEA 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 cases diagnosed two years after blood draw, myristoleic acid (OR = 1.37; 95%CI = 1.15-1.62; FDR = 0.072) and C60:12 triacylglycerol (OR = 0.75; 95%CI = 0.64-0.88; FDR = 0.072 were associated with CRC risk in women. WGCNA 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.</p><p><strong>Conclusions: </strong>We identified pre-diagnostic CRC-associated metabolites with distinct sex-specific profiles. These results provide insight into CRC etiopathogenesis and have implications for risk prediction strategies.</p>","PeriodicalId":14809,"journal":{"name":"JNCI Journal of the National Cancer Institute","volume":null,"pages":null},"PeriodicalIF":9.9000,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"JNCI Journal of the National Cancer Institute","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1093/jnci/djae270","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Metabolomic profiles may influence colorectal cancer (CRC) development. Few studies have performed pre-diagnostic metabolome-wide analyses with CRC risk.
Methods: We conducted a nested case-control study among women (Nurses' Health Study (NHS)) and men (Health Professionals Follow-up Study (HPFS)) who provided blood between 1989 and 1995. Over 22.9 years, 684 (409 NHS, 275 HPFS) incident CRC cases occurred and were matched 1:1 to controls. Liquid chromatography-mass spectrometry (LC-MS) identified 255 plasma metabolites after quality control. Cohort-specific and combined metabolite association analyses were performed using conditional logistic regression. Metabolite set enrichment analysis (MSEA) was used to identify differential abundance in metabolite classes. Weighted Correlation Network Analysis (WGCNA) provided modules of covarying metabolites, which were tested for CRC association.
Results: MSEA 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 cases diagnosed two years after blood draw, myristoleic acid (OR = 1.37; 95%CI = 1.15-1.62; FDR = 0.072) and C60:12 triacylglycerol (OR = 0.75; 95%CI = 0.64-0.88; FDR = 0.072 were associated with CRC risk in women. WGCNA 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.
Conclusions: We identified pre-diagnostic CRC-associated metabolites with distinct sex-specific profiles. These results provide insight into CRC etiopathogenesis and have implications for risk prediction strategies.
期刊介绍:
The Journal of the National Cancer Institute is a reputable publication that undergoes a peer-review process. It is available in both print (ISSN: 0027-8874) and online (ISSN: 1460-2105) formats, with 12 issues released annually. The journal's primary aim is to disseminate innovative and important discoveries in the field of cancer research, with specific emphasis on clinical, epidemiologic, behavioral, and health outcomes studies. Authors are encouraged to submit reviews, minireviews, and commentaries. The journal ensures that submitted manuscripts undergo a rigorous and expedited review to publish scientifically and medically significant findings in a timely manner.