title: Early detection of cancer in the general population: a blinded case-control study of p53 autoantibodies in colorectal cancer.
abstract: BACKGROUND
  Recent reports from cancer screening trials in high-risk populations suggest that autoantibodies can be detected before clinical diagnosis. However, there is minimal data on the role of autoantibody signatures in cancer screening in the general population.
  
  
  METHODS
  Informative p53 peptides were identified in sera from patients with colorectal cancer using an autoantibody microarray with 15-mer overlapping peptides covering the complete p53 sequence. The selected peptides were evaluated in a blinded case-control study using stored serum from the multimodal arm of the United Kingdom Collaborative Trial of Ovarian Cancer Screening where women gave annual blood samples. Cases were postmenopausal women who developed colorectal cancer following recruitment, with 2 or more serum samples preceding diagnosis. Controls were age-matched women with no history of cancer.
  
  
  RESULTS
  The 50 640 women randomised to the multimodal group were followed up for a median of 6.8 (inter-quartile range 5.9-8.4) years. Colorectal cancer notification was received in 101 women with serial samples of whom 97 (297 samples) had given consent for secondary studies. They were matched 1 : 1 with 97 controls (296 serial samples). The four most informative peptides identified 25.8% of colorectal cancer patients with a specificity of 95%. The median lead time was 1.4 (range 0.12-3.8) years before clinical diagnosis.
  
  
  CONCLUSIONS
  Our findings suggest that in the general population, autoantibody signatures are detectable during preclinical disease and may be of value in cancer screening. In colorectal cancer screening in particular, where the current need is to improve compliance, it suggests that p53 autoantibodies may contribute towards risk stratification.
authors.affiliation: Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen N, DK-2200, Denmark.
authors.forename: J W
authors.initials: JW
authors.lastname: Pedersen
authors.forename: A
authors.initials: A
authors.lastname: Gentry-Maharaj
authors.forename: E-O
authors.initials: EO
authors.lastname: Fourkala
authors.forename: A
authors.initials: A
authors.lastname: Dawnay
authors.forename: M
authors.initials: M
authors.lastname: Burnell
authors.forename: A
authors.initials: A
authors.lastname: Zaikin
authors.forename: A E
authors.initials: AE
authors.lastname: Pedersen
authors.forename: I
authors.initials: I
authors.lastname: Jacobs
authors.forename: U
authors.initials: U
authors.lastname: Menon
authors.forename: H H
authors.initials: HH
authors.lastname: Wandall
mesh_terms: D000368:Aged; D001323:Autoantibodies / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000175:diagnosis*; D055088:Early Detection of Cancer; D005260:Female; D006801:Humans; D008875:Middle Aged; D011159:Population Surveillance; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D014408:Biomarkers, Tumor; D016159:Tumor Suppressor Protein p53