Early detection of cancer in the general population: a blinded case-control study of p53 autoantibodies in colorectal cancer.

Publisher: Nature Publishing Group on behalf of Cancer Research UK Country of Publication: England NLM ID: 0370635 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1532-1827 (Electronic) Linking ISSN: 00070920 NLM ISO Abbreviation: Br J Cancer Subsets: MEDLINE

Publication: 2002- : London : Nature Publishing Group on behalf of Cancer Research UK
Original Publication: London, Lewis.

Early Detection of Cancer*; Autoantibodies/*analysis ; Colorectal Neoplasms/*diagnosis ; Tumor Suppressor Protein p53/*immunology; Aged ; Biomarkers, Tumor/analysis ; Case-Control Studies ; Female ; Humans ; Middle Aged ; Population Surveillance ; Sensitivity and Specificity

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.
Conclusion: 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.

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G0801228 United Kingdom MRC_ Medical Research Council; G9901012 United Kingdom MRC_ Medical Research Council; United Kingdom CRUK_ Cancer Research UK

0 (Autoantibodies)
0 (Biomarkers, Tumor)
0 (Tumor Suppressor Protein p53)

Date Created: 20121122 Date Completed: 20130307 Latest Revision: 20220129

20250114

PMC3553520

10.1038/bjc.2012.517

23169294