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Colonoscopy and Reduction of Colorectal Cancer Risk by Molecular Tumor Subtypes
TAKE-HOME MESSAGE
- The authors evaluated the effect of tumor markers on risk reduction of colorectal cancer (CRC) after colonoscopy in a case–control study. Weaker risk reduction was observed in patients with microsatellite-instable CRC (OR, 0.70), CpG island methylator phenotype–high CRC (OR, 0.45), BRAF-mutated CRC (OR, 0.62), KRAS-nonmutated CRC (OR, 0.34), and CRC classified into the sessile serrated pathway (OR, 0.57). The risk reduction was even weaker in proximal CRC.
- Although colonoscopy in general reduces the risk of CRC, molecular characterizations, the CRC pathway, and the location of adenomas impact the future risk of CRC.
– Judy A. Trieu, MD
abstract
This abstract is available on the publisher's site.
Access this abstract nowINTRODUCTION
In previous studies, the protective effect of colonoscopy was generally stronger for distal colorectal cancer than for proximal colorectal cancer (CRC). This study aimed to investigate whether reduction of CRC risk through colonoscopy varies according to major tumor markers and pathways of CRC.
METHODS
This is a population-based case-control study from Germany, including 2,132 patients with a first diagnosis of CRC and information on major molecular tumor markers and 2,486 control participants without CRC. Detailed participant characteristics were collected by standardized questionnaires. Information on previous colonoscopy was derived from medical records. Polytomous logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for the association between previous colonoscopy and subtypes of CRC.
RESULTS
Overall, we observed strong risk reduction of CRC after colonoscopy that was weaker for microsatellite instable (MSI) than for non-MSI CRC (OR 0.70, 95% CI 0.50-0.97 vs OR 0.28, 95% CI 0.24-0.33), for CpG island methylator phenotype high CRC than for CpG island methylator phenotype low/negative CRC (OR 0.45, 95% CI 0.34-0.59 vs OR 0.29, 95% CI 0.25-0.34), for BRAF-mutated than for BRAF nonmutated CRC (OR 0.62, 95% CI 0.42-0.91 vs OR 0.30, 95% CI 0.25-0.35), for KRAS nonmutated than for KRAS-mutated CRC (OR 0.34, 95% CI 0.29-0.40 vs OR 0.26, 95% CI 0.20-0.32), and for CRC classified into the sessile serrated pathway than for CRC of the traditional pathway (OR 0.57, 95% CI 0.36-0.91 vs OR 0.30, 95% CI 0.25-0.37). After colonoscopy with the detection of adenomas or hyperplastic polyps, no risk reduction was found for sessile serrated pathway CRC, MSI, and BRAF-mutated subtypes.
DISCUSSION
Our study extends the molecular understanding of existing differences in risk reduction of proximal and distal CRCs reported by previous studies and may imply important information for improving strategies for timely detection of relevant precursors.
Additional Info
Disclosure statements are available on the authors' profiles:
Colonoscopy and Reduction of Colorectal Cancer Risk by Molecular Tumor Subtypes: A Population-Based Case-Control Study
Am. J. Gastroenterol 2020 Aug 27;[EPub Ahead of Print], M Hoffmeister, H Bläker, L Jansen, E Alwers, EL Amitay, PR Carr, M Kloor, E Herpel, W Roth, J Chang-Claude, H BrennerFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
A number of studies have shown that the colorectal cancer preventive effects of screening colonoscopy are less strong for right-sided lesions than for the distal colon, and, in fact, some studies have not been able to show any protective effect for proximal advanced lesions or cancers. Some of this could be explained due to suboptimal bowel preps, which tend to affect more often this part of the colon. Another aspect is the more common presence of flat lesions in this section of the colon, which could result in a more difficult visualization for earlier lesions in particular. Often proximal, flatter adenocarcinomas have microsatellite instability (MSI) and methylation of CpG island regions (CIMP-high), and a significant number follow the serrated pathway of carcinogenesis with BRAF mutations as opposed to KRAS mutations. Data on the potential preventive effects according the main colorectal carcinogenic pathways are scarce.
In this study by Hoffmeister et al, the authors used a cohort of colorectal cancer patients from southwest Germany, whose tumors had been characterized by a carcinogenic pathway, to better understand any potential association between the molecular cancer type and the potential protective effect of screening colonoscopy. Control patients were recruited at the same time as cancer patients. The authors confirmed in their cohort a more protective effect for the proximal colon and, within this area, less protection for the molecular subtypes more commonly seen in the proximal colon, such as MSI/serrated pathway cancers. In fact, the weakest risk reduction seen in the MSI/CIMP/serrated pathway was mostly due to a weaker risk reduction in the proximal colon. Whether it is the unique carcinogenic processes, the morphological nature of these tumors, or the actual tumor location that determines the lesser effectiveness of colonoscopy screening, or a mix of them all, newer approaches may be required so patients who develop these tumors can benefit from screening.