Data from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study Article Swipe

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Henriette C. Jodal , Eddymurphy U. Akwiwu , Margriet Lemmens , Pien M. Delis‐van Diemen , Dagmar Klotz , Leticia G. León , Soufyan Lakbir , Meike de Wit , Remond J.A. Fijneman , Monique E. van Leerdam , Evelien Dekker , Manon C.W. Spaander , Gerrit A. Meijer , Magnus Løberg , Veerle M.H. Coupé , Mette Kalager , Beatriz Carvalho ·

YOU? · · 2023 · Open Access · · DOI: https://doi.org/10.1158/2767-9764.c.6927525.v1

Current morphologic 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 (CNAs) are associated with adenoma-to-carcinoma progression. We aimed to evaluate whether these molecular features can better predict an individual's risk of me-CRC than the morphologic advanced adenoma features.In this nested case–control study, 529 individuals with a single adenoma at first colonoscopy were selected from a Norwegian adenoma cohort. DNA copy-number profiles were determined, by low-coverage whole-genome sequencing. Prevalence of CNAs in advanced and non-advanced adenomas and its association (OR) with me-CRC was assessed. For the latter, cases (with me-CRC) were matched to controls (without me-CRC) on follow-up, age and sex.CNAs associated with adenoma-to-carcinoma progression were observed in 85/267 (32%) of advanced adenomas and in 27/262 (10%) of non-advanced adenomas. me-CRC was statistically significantly associated, also after adjustment for other variables, with age at baseline [OR, 1.14; 95% confidence interval CI), 1.03–1.26; P = 0.012], advanced adenomas (OR, 2.46; 95% CI, 1.50–4.01; P < 0.001) and with the presence of ≥3 DNA copy-number losses (OR, 1.90; 95% CI. 1.02–3.54; P = 0.043).Molecularly-defined high-risk adenomas were associated with me-CRC, but the association of advanced adenoma with me-CRC was stronger.Significance:Identifying new biomarkers may improve prediction of me-CRC for individuals with adenomas and optimize surveillance intervals to reduce risk of colorectal cancer and reduce oversurveillance of patients with low risk of colorectal cancer. Use of DNA CNAs alone does not improve prediction of me-CRC. Further research to improve risk classification is required.

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Adenoma Colorectal cancer Medicine Internal medicine Colorectal adenoma Confidence interval Oncology Dysplasia Colonoscopy Cancer Carcinoma Gastroenterology

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1158/2767-9764.c.6927525.v1
OA Status: gold
Related Works: 10
OpenAlex ID: https://openalex.org/W4388629379

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DOI: https://doi.org/10.1158/2767-9764.c.6927525.v1

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Title: Data from Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study

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Type: preprint

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Language: en

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Publication year: 2023

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Publication date: 2023-11-13

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Authors: Henriette C. Jodal, Eddymurphy U. Akwiwu, Margriet Lemmens, Pien M. Delis‐van Diemen, Dagmar Klotz, Leticia G. León, Soufyan Lakbir, Meike de Wit, Remond J.A. Fijneman, Monique E. van Leerdam, Evelien Dekker, Manon C.W. Spaander, Gerrit A. Meijer, Magnus Løberg, Veerle M.H. Coupé, Mette Kalager, Beatriz Carvalho

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Landing page: https://doi.org/10.1158/2767-9764.c.6927525.v1

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OA URL: https://doi.org/10.1158/2767-9764.c.6927525.v1

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Concepts: Adenoma, Colorectal cancer, Medicine, Internal medicine, Colorectal adenoma, Confidence interval, Oncology, Dysplasia, Colonoscopy, Cancer, Carcinoma, Gastroenterology

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abstract_inverted_index.evaluate	49
abstract_inverted_index.features	2, 53
abstract_inverted_index.interval	168
abstract_inverted_index.observed	135
abstract_inverted_index.optimize	229
abstract_inverted_index.patients	242
abstract_inverted_index.presence	187
abstract_inverted_index.profiles	90
abstract_inverted_index.research	261
abstract_inverted_index.selected	82
abstract_inverted_index.(me-CRC),	29
abstract_inverted_index.Norwegian	85
abstract_inverted_index.adenomas.	148
abstract_inverted_index.assessed.	112
abstract_inverted_index.dysplasia	10
abstract_inverted_index.high-risk	201
abstract_inverted_index.intervals	231
abstract_inverted_index.molecular	52
abstract_inverted_index.optimally	16
abstract_inverted_index.Prevalence	97
abstract_inverted_index.adjustment	156
abstract_inverted_index.associated	42, 130, 204
abstract_inverted_index.biomarkers	218
abstract_inverted_index.colorectal	27, 236, 247
abstract_inverted_index.component)	14
abstract_inverted_index.confidence	167
abstract_inverted_index.follow-up,	126
abstract_inverted_index.high-grade	9
abstract_inverted_index.prediction	221, 257
abstract_inverted_index.suboptimal	34
abstract_inverted_index.variables,	159
abstract_inverted_index.alterations	39
abstract_inverted_index.associated,	153
abstract_inverted_index.association	107, 209
abstract_inverted_index.colonoscopy	80
abstract_inverted_index.copy-number	38, 89, 191
abstract_inverted_index.determined,	92
abstract_inverted_index.distinguish	17
abstract_inverted_index.individuals	18, 73, 225
abstract_inverted_index.morphologic	1, 64
abstract_inverted_index.progression	133
abstract_inverted_index.sequencing.	96
abstract_inverted_index.1.02–3.54;	197
abstract_inverted_index.1.03–1.26;	170
abstract_inverted_index.1.50–4.01;	180
abstract_inverted_index.individual's	58
abstract_inverted_index.low-coverage	94
abstract_inverted_index.metachronous	26
abstract_inverted_index.non-advanced	103, 147
abstract_inverted_index.progression.	45
abstract_inverted_index.surveillance	230
abstract_inverted_index.whole-genome	95
abstract_inverted_index.significantly	152
abstract_inverted_index.statistically	151
abstract_inverted_index.surveillance.	35
abstract_inverted_index.case–control	70
abstract_inverted_index.classification	265
abstract_inverted_index.oversurveillance	240
abstract_inverted_index.<i>P</i>	171, 181, 198
abstract_inverted_index.adenoma-to-carcinoma	44, 132
abstract_inverted_index.sex.</p><p>CNAs	129
abstract_inverted_index.features.</p><p>In	67
abstract_inverted_index.required.</p></div>	267
abstract_inverted_index.<div>Abstract<p>Current	0
abstract_inverted_index.0.043).</p><p>Molecularly-defined	200
abstract_inverted_index.stronger.</p>Significance:<p>Identifying	216
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