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Long-Term Colorectal-Cancer Incidence and Mortality
after Lower Endoscopy
Supervisor: 邱宗傑 主任Presented by 郭政裕 總醫師
NEJM, Sep 19, 2013
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• Polyp-Cancer sequency ?
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Morphology, Anatomic Distribution and Cancer Potential of Colonic Polyps. Annals Surgery 1979;190:679-683.
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Morphology, Anatomic Distribution and Cancer Potential of Colonic Polyps. Annals Surgery 1979;190:679-683.
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Familiar adenomatous polyposis (FAP)
• APC mutations (Adenomatous polyposis coli) • An inherited cancer-predisposition syndrome• more than 100 adenomatous polyps • in carriers of the mutant gene, the risk of colorectal cancer by the age of 40 years is almost 100%
Kathleen H. Biology Of The APC Tumor Suppressor. J Clin Oncol 2000;18:1967-1979.
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• Animal model: • The Apcmin mouse – chemical mutagenesis that introduced a chain-
terminating mutation at nucleotide 2549 in mApc– develop numerous intestinal adenomas in which the
remaining wild-type allele is somatically inactivated during adenoma developmentKathleen H. Biology Of The APC Tumor Suppressor. J Clin Oncol 2000;18:1967-1979.
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Sporadic colorectal adenoma and cancers
• APC – Somatic mutations and
deletions that inactivate both copies of APC are present in most patients
• Wild-type APC– Mutations of β-catenin
resistent to the β-catenin degradation complex Kathleen H. Biology Of The APC Tumor Suppressor. J Clin Oncol 2000;18:1967-1979.
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Sanford D. Moleucular Basis of Colorectal Cancer. N Engl J Med 2009;361:2449-60.
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Sanford D. Moleucular Basis of Colorectal Cancer. N Engl J Med 2009;361:2449-60.
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Methods
• Study population– Prospective cohort study
• The Nurses’ Health Study: 121,700 U.S. female nurses (30~55 y/o), since 1976
• The Health Professionals Follow-up Study: 51,529 U.S. male health professionals (40~75 y/o), sinc 1986
• Exclusion criteria– History of cancer– Ulcerative colitis– Colorectal polyps– Familiar polyposis syndromes– Previous lower endoscopy
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• Observational studies– Enrolled: n=88,902 (31,736 men, 57,166 women)– 1998~2008– Questionnaire and collect information every 2
year (Low GI endoscopy: sigmoidscopy or colonoscopy)
– Incidence analysis in 2010, mortality analysis in 2012
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• Polyps– Adenomatous polyps – Advanced adenoma (≥10 mm, tubulovillus or
villous, or high-grade dysplasia)– High-risk adenoma ( numbers ≥ 3)– Colonoscopic polypectomy: excision of comfirmed
adenomatous polyps (excluding hyperplastic polyps)
– Negative endoscopy: no adenomas or CRCs
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• Molecular analysis – Microsatellite instability status– BRAF (codon 600)– KRAS (codon 12 and 13)– PIK3CA (exons 9 and 20)– DNA methylation (8 CpG island methylator
phenotype, CIMP)• Specific promotors: MLH1, CACNA1G, CDKN2A, CRABP1,
IGF2, NEUROG1, RUNX3, and SOCS1)• Long interspersed nucleotide element 1 (LINE-1)
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Results
• 88,902 participants, follow-up for 22 years– Received endoscopy vs. without endoscopy– Colorectal cancer: 1815 incident cases (2%)
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Screen colonscopy interval
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Surveillance colonoscopy interval after removal of adenomatous polyps
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Summary
• Low gastrointestinal endoscopy is associated with a low incidence and low mortality of colorectal cancer
• Tumor molecular features of the serrated pathway might be involved in the development of cancer within 5 years after colonoscopy
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Thanks for your attention!