title: A prospective study of serum metabolites and colorectal cancer risk.
abstract: BACKGROUND
  Colorectal cancer is highly prevalent, and the vast majority of cases are thought to be sporadic, although few risk factors have been identified. Using metabolomics technology, our aim was to identify biomarkers prospectively associated with colorectal cancer.
  
  
  METHODS
  This study included 254 incident colorectal cancers and 254 matched controls nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Serum samples were collected at baseline, and the mean length of follow-up was 8 years. Serum metabolites were analyzed by ultra-high performance liquid-phase chromatography with tandem mass spectrometry, and gas chromatography coupled with mass spectrometry. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for metabolites above the limit of detection and present in at least 80% of participants.
  
  
  RESULTS
  A total of 676 serum metabolites were measured; of these, 447 were of known identity and 278 of these were present in >80% of individuals. Overall, there was no association between serum metabolites and colorectal cancer; however, some suggestive associations were observed between individual metabolites and colorectal cancer but none reached statistical significance after Bonferroni correction for multiple comparisons. For example, leucyl-leucine was inversely associated (OR comparing the 90th to the 10th percentile = 0.50; 95% CI = 0.32-0.80; P = .003). In sex-stratified analyses, serum glycochenodeoxycholate was positively associated with colorectal cancer among women (OR(90th vs.10th percentile)  = 5.34; 95% CI = 2.09-13.68; P = .0001).
  
  
  CONCLUSIONS
  No overall associations were observed between serum metabolites and colorectal cancer, but serum glycochenodeoxycholate, a bile acid metabolite, was positively associated with colorectal cancer among women.
authors.affiliation: Department of Epidemiology and Biostatistics, School of Public Health, Faculty of Medicine, Imperial College London, London, United Kingdom.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cross
authors.forename: Steven C
authors.initials: SC
authors.lastname: Moore
authors.forename: Simina
authors.initials: S
authors.lastname: Boca
authors.forename: Wen-Yi
authors.initials: WY
authors.lastname: Huang
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Xiong
authors.forename: Rachael
authors.initials: R
authors.lastname: Stolzenberg-Solomon
authors.forename: Rashmi
authors.initials: R
authors.lastname: Sinha
authors.forename: Joshua N
authors.initials: JN
authors.lastname: Sampson
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid; D015179:Colorectal Neoplasms / Q000097:blood*; D004151:Dipeptides / Q000097:blood; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D008401:Gas Chromatography-Mass Spectrometry; D005999:Glycochenodeoxycholic Acid / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011446:Prospective Studies; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D014408:Biomarkers, Tumor; D004151:Dipeptides; C038361:leucylleucine; D005999:Glycochenodeoxycholic Acid
keywords: biomarkers; colorectal cancer; epidemiology; mass spectrometry; metabolites; metabolomics