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International Journal of Colorectal Disease
Erschienen in:

22.10.2016 | Original Article

Case-control study of candidate gene methylation and adenomatous polyp formation

verfasst von: M. Alexander, J. B. Burch, S. E. Steck, C.-F. Chen, T. G. Hurley, P. Cavicchia, N. Shivappa, J. Guess, H. Zhang, S. D. Youngstedt, K. E. Creek, S. Lloyd, K. Jones, J. R. Hébert

Erschienen in: International Journal of Colorectal Disease | Ausgabe 2/2017

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Abstract

Purpose

Colorectal cancer (CRC) is one of the most common and preventable forms of cancer but remains the second leading cause of cancer-related death. Colorectal adenomas are precursor lesions that develop in 70–90 % of CRC cases. Identification of peripheral biomarkers for adenomas would help to enhance screening efforts. This exploratory study examined the methylation status of 20 candidate markers in peripheral blood leukocytes and their association with adenoma formation.

Methods

Patients recruited from a local endoscopy clinic provided informed consent and completed an interview to ascertain demographic, lifestyle, and adenoma risk factors. Cases were individuals with a histopathologically confirmed adenoma, and controls included patients with a normal colonoscopy or those with histopathological findings not requiring heightened surveillance (normal biopsy, hyperplastic polyp). Methylation-specific polymerase chain reaction was used to characterize candidate gene promoter methylation. Odds ratios (ORs) and 95 % confidence intervals (95% CIs) were calculated using unconditional multivariable logistic regression to test the hypothesis that candidate gene methylation differed between cases and controls, after adjustment for confounders.

Results

Complete data were available for 107 participants; 36 % had adenomas (men 40 %, women 31 %). Hypomethylation of the MINT1 locus (OR 5.3, 95% CI 1.0–28.2) and the PER1 (OR 2.9, 95% CI 1.1–7.7) and PER3 (OR 11.6, 95% CI 1.6–78.5) clock gene promoters was more common among adenoma cases. While specificity was moderate to high for the three markers (71–97 %), sensitivity was relatively low (18–45 %).

Conclusion

Follow-up of these epigenetic markers is suggested to further evaluate their utility for adenoma screening or surveillance.
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Metadaten
Titel
Case-control study of candidate gene methylation and adenomatous polyp formation
verfasst von
M. Alexander
J. B. Burch
S. E. Steck
C.-F. Chen
T. G. Hurley
P. Cavicchia
N. Shivappa
J. Guess
H. Zhang
S. D. Youngstedt
K. E. Creek
S. Lloyd
K. Jones
J. R. Hébert
Publikationsdatum
22.10.2016
Verlag
Springer Berlin Heidelberg
Erschienen in
International Journal of Colorectal Disease / Ausgabe 2/2017
Print ISSN: 0179-1958
Elektronische ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-016-2688-1

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