Untargeted Lipidomic Features Associated with Colorectal Cancer in a Prospective Cohort

Details

• Personal Author:
  Cai X ; Dudoit S ; Edmands WMB ; Grigoryan H ; Gunter MJ ; Naccarati A ; Perttula K ; Petrick L ; Polidoro S ; Rappaport SM ; Schiffman C ; Vineis P
• Description:
  Background: Epidemiologists are beginning to employ metabolomics and lipidomics with archived blood from incident cases and controls to discover causes of cancer. Although several such studies have focused on colorectal cancer (CRC), they all followed targeted or semi-targeted designs that limited their ability to find discriminating molecules and pathways related to the causes of CRC. Methods: Using an untargeted design, we measured lipophilic metabolites in prediagnostic serum from 66 CRC patients and 66 matched controls from the European Prospective Investigation into Cancer and Nutrition (Turin, Italy). Samples were analyzed by liquid chromatography-high-resolution mass spectrometry (LC-MS), resulting in 8690 features for statistical analysis. Results: Rather than the usual multiple-hypothesis-testing approach, we based variable selection on an ensemble of regression methods, which found nine features to be associated with case-control status. We then regressed each selected feature on time-to-diagnosis to determine whether the feature was likely to be either a potentially causal biomarker or a reactive product of disease progression (reverse causality). Conclusions: Of the nine selected LC-MS features, four appear to be involved in CRC etiology and merit further investigation in prospective studies of CRC. Four other features appear to be related to progression of the disease (reverse causality), and may represent biomarkers of value for early detection of CRC. [Description provided by NIOSH]
• Subjects:
  Biomarkers Blood Energy Metabolism Epidemiology Neoplasms Occupational Health Safety
• Keywords:
  Author Keywords: Colorectal Cancer Cancer Colorectal Cancer EPIC Etiology Lipidomics Liquid Chromatography Mass Spectrometry Metabolites Metabolomics Samplers Untargeted

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• ISSN:
  1471-2407
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; New York ; OSHA Region 2 ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  18
• Issue:
  1
• NIOSHTIC Number:
  nn:20055301
• Citation:
  BMC Cancer 2018 Oct; 18(1):996
• Contact Point Address:
  Stephen M Rappaport, School of Public Health, University of California, Berkeley, CA 94720-7356
• Email:
  srappaport@berkeley.edu
• Federal Fiscal Year:
  2019
• Performing Organization:
  University of California, Berkeley
• Peer Reviewed:
  True
• Start Date:
  20050701
• Source Full Name:
  BMC Cancer
• End Date:
  20250630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:660af5b5c2189d0b72e980c67e3bb61f3668c87574f4a8c12412cbd49f5e470b66cb26e078531e3be0cab0ed2f9c9b452ca569d2661bd72645688f4880215b9a
• Download URL:
  https://stacks.cdc.gov/view/cdc/217639/cdc_217639_DS1.pdf
• File Type:
  [PDF - 1.06 MB ]