Dataset Information

Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case-control study.

ABSTRACT:

Background

Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs).

Methods

Whole-genome chromosomal copy number changes and mutation status of genes commonly affected in CRC were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status was also determined.

Results

In total, 122 PCCRCs and 98 DCRCs with high-quality DNA were examined. PCCRCs were more often located proximally (P < 0.001), non-polypoid appearing (P = 0.004), early stage (P = 0.009) and poorly differentiated (P = 0.006). PCCRCs showed significantly less 18q loss (FDR < 0.2), compared to DCRCs. No significant differences in mutations were observed. PCCRCs were more commonly CIMP high (P = 0.014) and MSI (P = 0.029). After correction for tumour location, only less 18q loss remained significant (P = 0.005).

Conclusion

Molecular features associated with the sessile serrated lesions (SSLs) and non-polypoid colorectal neoplasms (CRNs) are more commonly seen in PCCRCs than in DCRCs. These together with the clinical features observed support the hypothesis that SSLs and non-polypoid CRNs are contributors to the development of PCCRCs. The future focus should be directed at improving the detection and endoscopic removal of these non-polypoid CRN and SSLs.

Clinical trial registration

NTR3093 in the Dutch trial register ( www.trialregister.nl ).

SUBMITTER: Bogie RMM

PROVIDER: S-EPMC8927607 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case-control study.

Bogie Roel M M RMM le Clercq Chantal M C CMC Voorham Quirinus J M QJM Cordes Martijn M Sie Daoud D Rausch Christian C van den Broek Evert E de Vries Sara D J SDJ van Grieken Nicole C T NCT Riedl Robert G RG Sastrowijoto Prapto P Speel Ernst-Jan EJ Vos Rein R Winkens Bjorn B van Engeland Manon M Ylstra Bauke B Meijer Gerrit A GA Masclee Ad A M AAM Carvalho Beatriz B

British journal of cancer 20211215 6

<h4>Background</h4>Post-colonoscopy colorectal cancers (PCCRCs) pose challenges in clinical practice. PCCRCs occur due to a combination of procedural and biological causes. In a nested case-control study, we compared clinical and molecular features of PCCRCs and detected CRCs (DCRCs).<h4>Methods</h4>Whole-genome chromosomal copy number changes and mutation status of genes commonly affected in CRC were examined by low-coverage WGS and targeted sequencing, respectively. MSI and CIMP status was als ...[more]

PMID: 34912077

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Project description:ObjectivesThe aim of this study was to compare the morphology, radiological stage, conspicuity, and computer-assisted detection (CAD) characteristics of colorectal cancers (CRC) detected by computed tomographic colonography (CTC) in screening and symptomatic populations.MethodsTwo radiologists independently analyzed CTC images from 133 patients diagnosed with CRC in (a) two randomized trials of symptomatic patients (35 patients with 36 tumours) and (b) a screening program using fecal occult blood testing (FOBt; 98 patients with 100 tumours), measuring tumour length, volume, morphology, radiological stage, and subjective conspicuity. A commercial CAD package was applied to both datasets. We compared CTC characteristics between screening and symptomatic populations with multivariable regression.ResultsScreen-detected CRC were significantly smaller (mean 3.0 vs 4.3 cm, p < 0.001), of lower volume (median 9.1 vs 23.2 cm3, p < 0.001) and more frequently polypoid (34/100, 34 % vs. 5/36, 13.9 %, p = 0.02) than symptomatic CRC. They were of earlier stage than symptomatic tumours (OR = 0.17, 95 %CI 0.07-0.41, p < 0.001), and were judged as significantly less conspicuous (mean conspicuity 54.1/100 vs. 72.8/100, p < 0.001). CAD detection was significantly lower for screen-detected (77.4 %; 95 %CI 67.9-84.7 %) than symptomatic CRC (96.9 %; 95 %CI 83.8-99.4 %, p = 0.02).ConclusionsScreen-detected CRC are significantly smaller, more frequently polypoid, subjectively less conspicuous, and less likely to be identified by CAD than those in symptomatic patients.Key points• Screen-detected colorectal cancers (CRC) are significantly smaller than symptomatic CRC. • Screening cases are significantly less conspicuous to radiologists than symptomatic tumours. • Screen-detected CRC have different morphology compared to symptomatic tumours (more polypoid, fewer annular). • A commercial computer-aided detection (CAD) system was significantly less likely to note screen-detected CRC.

Project description:The effectiveness of screening colonoscopy in average-risk adults is uncertain, particularly for right colon cancer.To examine the association between screening colonoscopy and risk for incident late-stage colorectal cancer (CRC).Nested case-control study.Four U.S. health plans.1039 average-risk adults enrolled for at least 5 years in one of the health plans. Case patients were aged 55 to 85 years on their diagnosis date (reference date) of stage IIB or higher (late-stage) CRC during 2006 to 2008. One or 2 control patients were selected for each case patient, matched on birth year, sex, health plan, and prior enrollment duration.Receipt of CRC screening 3 months to 10 years before the reference date, ascertained through medical record audits. Case patients and control patients were compared on receipt of screening colonoscopy or sigmoidoscopy by using conditional logistic regression that accounted for health history, socioeconomic status, and other screening exposures.In analyses restricted to 471 eligible case patients and their 509 matched control patients, 13 case patients (2.8%) and 46 control patients (9.0%) had undergone screening colonoscopy, which corresponded to an adjusted odds ratio (AOR) of 0.29 (95% CI, 0.15 to 0.58) for any late-stage CRC, 0.36 (CI, 0.16 to 0.80) for right colon cancer, and 0.26 (CI, 0.06 to 1.11; P = 0.069) for left colon/rectum cancer. Ninety-two case patients (19.5%) and 173 control patients (34.0%) had screening sigmoidoscopy, corresponding to an AOR of 0.50 (CI, 0.36 to 0.70) overall, 0.79 (CI, 0.51 to 1.23) for right colon late-stage cancer, and 0.26 (CI, 0.14 to 0.48) for left colon cancer.The small number of screening colonoscopies affected the precision of the estimates.Screening with colonoscopy in average-risk persons was associated with reduced risk for diagnosis of incident late-stage CRC, including right-sided colon cancer. For sigmoidoscopy, this association was seen for left CRC, but the association for right colon late-stage cancer was not statistically significant.

Dataset Information

Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case-control study.

Background

Methods

Results

Conclusion

Clinical trial registration

Publications

Molecular pathways in post-colonoscopy versus detected colorectal cancers: results from a nested case-control study.

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