Elena M Stoffel1, Rune Erichsen2, Trine Frøslev2, Lars Pedersen2, Mogens Vyberg3, Erika Koeppe4, Seth D Crockett5, Stanley R Hamilton6, Henrik T Sørensen2, John A Baron5. 1. Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan; Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. Electronic address: estoffel@med.umich.edu. 2. Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark. 3. Institute of Pathology, Department of Clinical Medicine, Aalborg University Hospital, Aalborg, Denmark. 4. Department of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan. 5. Department of Internal Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 6. Division of Pathology and Laboratory Medicine, The University of Texas, MD Anderson Cancer Center, Houston, Texas.
Abstract
BACKGROUND & AIMS: Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy. METHODS: We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (dMMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation. RESULTS: Of 10,365 incident CRCs, 725 occurred after colonoscopy examinations (7.0%). These were more often located in the proximal colon (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.90-2.89) and were more likely to have dMMR (OR, 1.26; 95% CI, 1.00-1.59), but were less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89) compared with CRCs diagnosed in patients with no prior colonoscopy. The highest proportions of proximal and/or dMMR tumors were observed in CRCs diagnosed 3-6 years after colonoscopy, but these features were still more frequent among cancers diagnosed up to 10 years after colonoscopy. The relative excess of dMMR tumors was most pronounced in distal cancers. In an analysis of 85 cases detected after colonoscopy, we found BRAF mutations in 23% of tumors and that 7% of cases had features of Lynch syndrome. Colonoscopy exams were incomplete in a higher proportion of cases diagnosed within <1 year (in 38%) than in those diagnosed within 1-10 years after colonoscopy (16%). CONCLUSIONS: In a study of incident CRC cases in Denmark, we observed that tumors found in patients who have undergone colonoscopy are more often proximal and have dMMR compared to CRCs detected in patients without previous colonoscopies. The excess of right-sided tumors and the modest independent effects of dMMR reinforce the importance of proper colonoscopic examination of the proximal large bowel.
BACKGROUND & AIMS: Colonoscopy provides incomplete protection from colorectal cancer (CRC), but determinants of post-colonoscopy CRC are not well understood. We compared clinical features and molecular characteristics of CRCs diagnosed at different time intervals after a previous colonoscopy. METHODS: We performed a population-based, cross-sectional study of incident CRC cases in Denmark (2007-2011), categorized as post-colonoscopy or detected during diagnostic colonoscopy (in patients with no prior colonoscopy). We compared prevalence of proximal location and DNA mismatch repair deficiency (dMMR) in CRC tumors, relative to time since previous colonoscopy, using logistic regression and cubic splines to assess temporal variation. RESULTS: Of 10,365 incident CRCs, 725 occurred after colonoscopy examinations (7.0%). These were more often located in the proximal colon (odds ratio [OR], 2.34; 95% confidence interval [CI], 1.90-2.89) and were more likely to have dMMR (OR, 1.26; 95% CI, 1.00-1.59), but were less likely to be metastatic at presentation (OR, 0.65; 95% CI, 0.48-0.89) compared with CRCs diagnosed in patients with no prior colonoscopy. The highest proportions of proximal and/or dMMRtumors were observed in CRCs diagnosed 3-6 years after colonoscopy, but these features were still more frequent among cancers diagnosed up to 10 years after colonoscopy. The relative excess of dMMRtumors was most pronounced in distal cancers. In an analysis of 85 cases detected after colonoscopy, we found BRAF mutations in 23% of tumors and that 7% of cases had features of Lynch syndrome. Colonoscopy exams were incomplete in a higher proportion of cases diagnosed within <1 year (in 38%) than in those diagnosed within 1-10 years after colonoscopy (16%). CONCLUSIONS: In a study of incident CRC cases in Denmark, we observed that tumors found in patients who have undergone colonoscopy are more often proximal and have dMMR compared to CRCs detected in patients without previous colonoscopies. The excess of right-sided tumors and the modest independent effects of dMMR reinforce the importance of proper colonoscopic examination of the proximal large bowel.
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