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  • Articles  (2)
  • The American Association for Cancer Research (AACR)  (1)
  • The American Association for Clinical Chemistry (AACC)  (1)
  • German Medical Science; Düsseldorf, Köln
  • 2015-2019  (2)
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  • Articles  (2)
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  • 1
    Publication Date: 2018-02-10
    Description: Background: The presence of circulating antibodies to the p53 tumor suppressor protein is a potential early detection colorectal cancer biomarker. However, studies of prediagnostic measures of p53 seropositivity in relation to colorectal cancer risk are limited. Methods: We conducted a nested case–control study of serum p53 autoantibodies and risk of colorectal cancer within the Cancer Prevention Study-II Nutrition Cohort. Among cohort participants who were cancer free at the time of blood collection, 392 were subsequently diagnosed with colorectal cancer over 11 years of follow-up. Two controls were matched to each case on birth date, blood draw date, race, and sex. Autoantibodies to p53 were detected in 41 of the 392 cases (10.5%) and 49 of the 774 controls (6.3%). Results: Participants who were seropositive for p53 antibodies before diagnosis were more likely to be subsequently diagnosed with colorectal cancer [RR = 1.77; 95% confidence interval (CI), 1.12–2.78]. This association was strongest within 3 years of diagnosis (RR = 2.26; 95% CI, 1.06–4.83). An association was also suggested when colorectal cancer was diagnosed 4 to 〈6 years after p53 measurement (RR = 1.84; 95% CI, 0.89–3.79), but not 6 or more years later (RR = 1.15; 95% CI, 0.44–2.99). Conclusions: If these results are confirmed, serum p53 antibodies may be useful on a panel of early detection markers for colorectal cancer. Impact: Individuals who were seropositive for p53 antibodies were twice as likely to develop colorectal cancer within the next 3 years compared with those who were seronegative. This marker is a good candidate for inclusion on an early detection marker panel for colorectal cancer. Cancer Epidemiol Biomarkers Prev; 27(2); 219–23. ©2017 AACR .
    Print ISSN: 1055-9965
    Electronic ISSN: 1538-7755
    Topics: Medicine
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  • 2
    Publication Date: 2018-01-30
    Description: BACKGROUND: Progress in the liquid biopsy field, combined with the development of droplet digital PCR (ddPCR), has enabled noninvasive monitoring of mutations with high detection accuracy. However, current assays detect a restricted number of mutations per reaction. ddPCR is a recognized method for detecting alterations previously characterized in tumor tissues, but its use as a discovery tool when the mutation is unknown a priori remains limited. METHODS: We established 2 ddPCR assays detecting all genomic alterations within KRAS exon 2 and EGFR exon 19 mutation hotspots, which are of clinical importance in colorectal and lung cancer, with use of a unique pair of TaqMan ® oligoprobes. The KRAS assay scanned for the 7 most common mutations in codons 12/13 but also all other mutations found in that region. The EGFR assay screened for all in-frame deletions of exon 19, which are frequent EGFR-activating events. RESULTS: The KRAS and EGFR assays were highly specific and both reached a limit of detection of 〈0.1% in mutant allele frequency. We further validated their performance on multiple plasma and formalin-fixed and paraffin-embedded tumor samples harboring a panel of different KRAS or EGFR mutations. CONCLUSIONS: This method presents the advantage of detecting a higher number of mutations with single-reaction ddPCRs while consuming a minimum of patient sample. This is particularly useful in the context of liquid biopsy because the amount of circulating tumor DNA is often low. This method should be useful as a discovery tool when the tumor tissue is unavailable or to monitor disease during therapy.
    Keywords: Cancer Diagnostics (since 2002)
    Print ISSN: 0009-9147
    Electronic ISSN: 1530-8561
    Topics: Medicine
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