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

Henriette C. Jodal; Eddymurphy U. Akwiwu; Margriet Lemmens; Pien M. Delis-van Diemen; Dagmar Klotz; Leticia G. Leon; 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

doi:10.1158/2767-9764.CRC-23-0186

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

Henriette C. Jodal, Eddymurphy U. Akwiwu, Margriet Lemmens, Pien M. Delis-van Diemen, Dagmar Klotz, Leticia G. Leon, 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^*

^*Corresponding author for this work

Vrije Universiteit Amsterdam

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

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.

Original language	English
Pages (from-to)	2292-2301
Journal	Cancer Research Communications
Volume	3
Issue number	11
DOIs	https://doi.org/10.1158/2767-9764.CRC-23-0186
Publication status	Published - 13 Nov 2023
Externally published	Yes

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Jodal, H. C., Akwiwu, E. U., Lemmens, M., Diemen, P. M. D., Klotz, D., Leon, L. G., Lakbir, S., de Wit, M., Fijneman, R. J. A., van Leerdam, M. E., Dekker, E., Spaander, M. C. W., Meijer, G. A., Løberg, M., Coupé, V. M. H., Kalager, M., & Carvalho, B. (2023). Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study. Cancer Research Communications, 3(11), 2292-2301. https://doi.org/10.1158/2767-9764.CRC-23-0186

@article{f274bf3b7117493d9becb64f82c3e35e,

title = "Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study",

abstract = "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.",

author = "Jodal, {Henriette C.} and Akwiwu, {Eddymurphy U.} and Margriet Lemmens and Diemen, {Pien M. Delis-van} and Dagmar Klotz and Leon, {Leticia G.} and Soufyan Lakbir and {de Wit}, Meike and Fijneman, {Remond J.A.} and {van Leerdam}, {Monique E.} and Evelien Dekker and Spaander, {Manon C.W.} and Meijer, {Gerrit A.} and Magnus L{\o}berg and Coup{\'e}, {Veerle M.H.} and Mette Kalager and Beatriz Carvalho",

year = "2023",

month = nov,

day = "13",

doi = "10.1158/2767-9764.CRC-23-0186",

language = "English",

volume = "3",

pages = "2292--2301",

journal = "Cancer Research Communications",

issn = "2767-9764",

publisher = "American Association for Cancer Research Inc.",

number = "11",

}

Jodal, HC, Akwiwu, EU, Lemmens, M, Diemen, PMD, Klotz, D, Leon, LG, Lakbir, S, de Wit, M, Fijneman, RJA, van Leerdam, ME, Dekker, E, Spaander, MCW, Meijer, GA, Løberg, M, Coupé, VMH, Kalager, M & Carvalho, B 2023, 'Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas: A Nested Case–Control Study', Cancer Research Communications, vol. 3, no. 11, pp. 2292-2301. https://doi.org/10.1158/2767-9764.CRC-23-0186

TY - JOUR

T1 - Risk Prediction of Metachronous Colorectal Cancer from Molecular Features of Adenomas

T2 - A Nested Case–Control Study

AU - Jodal, Henriette C.

AU - Akwiwu, Eddymurphy U.

AU - Lemmens, Margriet

AU - Diemen, Pien M. Delis-van

AU - Klotz, Dagmar

AU - Leon, Leticia G.

AU - Lakbir, Soufyan

AU - de Wit, Meike

AU - Fijneman, Remond J.A.

AU - van Leerdam, Monique E.

AU - Dekker, Evelien

AU - Spaander, Manon C.W.

AU - Meijer, Gerrit A.

AU - Løberg, Magnus

AU - Coupé, Veerle M.H.

AU - Kalager, Mette

AU - Carvalho, Beatriz

PY - 2023/11/13

Y1 - 2023/11/13

N2 - 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.

AB - 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.

U2 - 10.1158/2767-9764.CRC-23-0186

DO - 10.1158/2767-9764.CRC-23-0186

M3 - Article

SN - 2767-9764

VL - 3

SP - 2292

EP - 2301

JO - Cancer Research Communications

JF - Cancer Research Communications

IS - 11

ER -

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

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