Antioxidant Supplement and Reduction of Metachronous Adenomas of the Large Bowel: a Double Blind Randomized Trial
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Adenomas,Colorectal Cancer,Adenoma
PROVIDER: 2113090 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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This will determine the feasibility of developing a large randomised trial of selenium to reduce the recurrence rates for advanced adenomas in NZ.
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Project description:"Background & Aims: Current morphological features defining advanced adenomas (size ≥10 mm, high grade dysplasia or >25% villous component) cannot optimally distinguish individuals at high-risk or low-risk of metachronous colorectal cancer (me-CRC), which may result in suboptimal surveillance. Certain DNA copy number alterations are associated with adenoma-to-carcinoma progression (cancer-associated events; CAEs). We aimed to evaluate whether CAEs can better predict an individual’s risk of me-CRC than the morphological advanced adenoma features.
Methods: In this nested case-control study, 529 individuals with a single adenoma at their first colonoscopy were selected from a Norwegian adenoma cohort. DNA copy number profiles were determined, by means of low-coverage whole genome sequencing. We assessed the prevalence of CAEs in advanced and non-advanced adenomas and its association with me-CRC. For the latter, cases (with CRC) were matched to controls (without CRC), with the same follow-up period as cases, as well as age and sex. Subsequently, odds ratios (OR) for the association of the presence of an advanced adenoma or a molecularly-defined high-risk adenoma with me-CRC were calculated.
Results: Molecular high-risk features were observed in 85/267 (32%) of advanced adenomas and in 27/262 (10%) of non-advanced adenomas. Me-CRC was more strongly associated with advanced adenomas (OR 3.58; 95% CI 2.27-5.72) than with molecular high-risk adenomas (OR 1.90; 95% CI 1.14–3.16). After adjusting for other variables, only advanced adenoma remained significantly associated with me-CRC (OR 3.39; 95% CI 2.10–5.55).
Conclusion: Molecularly-defined high-risk adenomas were associated with me-CRC, but the association of advanced adenoma with me-CRC was stronger. "
Project goal: Evaluate the value of DNA copy numbers alterations detected in a baseline adenoma, in the prediction of risk of metachronous CRC
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