Colonoscopy and reduction of colorectal cancer risk by molecular tumor subtypes: a population-based case-control study

Abstract

AbstractObjectiveIn previous studies, the protective effect of colonoscopy was generally stronger for distal than for proximal colorectal cancer (CRC). This study aimed to investigate whether the association of colonoscopy and CRC risk varies according to major molecular pathological features and pathways of CRC.DesignPopulation-based case-control study from Germany, including 2132 patients with a first diagnosis of CRC and information on major molecular tumor markers, and 2486 control participants without CRC. Detailed participant characteristics were collected by standardized questionnaires and information on previous colonoscopy was derived from medical records. Polytomous logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (95% CI) for the association between previous colonoscopy and subtypes of CRC.ResultsOverall, we observed strong risk reduction of CRC after colonoscopy that was weaker for microsatellite instable (MSI) than for non-MSI CRC (p for heterogeneity <0.01), for CpG island methylator phenotype (CIMP) high CRC than for CIMP low/negative CRC (p het<0.01), for BRAF-mutated than for BRAF non-mutated CRC (p het=0.01), for KRAS non-mutated than for KRAS-mutated CRC (p het=0.04), and for CRC classified into the sessile serrated pathway than for CRC of the traditional pathway (p het<0.01). After colonoscopy with detection of adenomas, no risk reduction was found for sessile serrated pathway CRC.ConclusionOur study extends the molecular understanding of existing differences in risk reduction of proximal and distal CRC reported by previous studies, and may imply important information for improving strategies for timely detection of relevant precursors.Summary BoxWhat is already known about this subject?Colonoscopy is an effective tool not only for early detection but also for prevention of colorectal cancer.In previous studies, risk reduction after colonoscopy was generally stronger for cancer of the distal colon and rectum than for cancer of the proximal colon.What are the new findings?This observational study found variation of colorectal cancer risk reduction after colonoscopy according to major molecular subtypes characteristic of the proximal colon (MSI, CIMP-high, BRAF mutation), and for colorectal cancer potentially developing via the sessile serrated pathway.How might it impact on clinical practice in the foreseeable future?This study contributes to the identification of molecular characteristics and associated phenotypes of potentially missed or more aggressive precursors.The study provides important information for improving strategies for a timely detection of relevant precursors at colonoscopy.