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 - Delis-van Diemen, Pien M
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
N1 - Publisher Copyright:
© 2023 The Authors.
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-tocarcinoma 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 profileswere determined, by low-coveragewhole-genome sequencing. Prevalence of CNAs in advanced and non-advanced adenomas and its association (OR) with me-CRC was assessed. For the latter, cases (withme-CRC) were matched to controls (withoutme-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 nonadvanced 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-tocarcinoma 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 profileswere determined, by low-coveragewhole-genome sequencing. Prevalence of CNAs in advanced and non-advanced adenomas and its association (OR) with me-CRC was assessed. For the latter, cases (withme-CRC) were matched to controls (withoutme-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 nonadvanced 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.
UR - http://www.scopus.com/inward/record.url?scp=85195201068&partnerID=8YFLogxK
U2 - 10.1158/2767-9764.crc-23-0186
DO - 10.1158/2767-9764.crc-23-0186
M3 - Article
C2 - 37921412
SN - 2767-9764
VL - 3
SP - 2292
EP - 2301
JO - Cancer Research Communications
JF - Cancer Research Communications
IS - 11
ER -
