Long-Term Colorectal-Cancer Incidence and Mortality after Lower Endoscopy

1. 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

2. Polyp-Cancer sequency ?

4. Morphology, Anatomic Distribution and Cancer Potential of Colonic Polyps. Annals Surgery 1979;190:679-683.

5. Morphology, Anatomic Distribution and Cancer Potential of Colonic Polyps. Annals Surgery 1979;190:679-683.

6. Familiar adenomatouspolyposis (FAP) • APC mutations (Adenomatouspolyposis coli) • An inherited cancer-predisposition syndrome • more than 100 adenomatouspolyps • 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 ClinOncol2000;18:1967-1979.

8. Animal model: • The Apcminmouse • 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 development Kathleen H. Biology Of The APC Tumor Suppressor. J ClinOncol2000;18:1967-1979.

9. 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 ClinOncol2000;18:1967-1979.

10. Sanford D. Moleucular Basis of Colorectal Cancer. N Engl J Med 2009;361:2449-60.

11. Sanford D. Moleucular Basis of Colorectal Cancer. N Engl J Med 2009;361:2449-60.

13. 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

14. 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

15. Polyps • Adenomatous polyps • Advanced adenoma (≥10 mm, tubulovillus or villous, or high-grade dysplasia) • High-risk adenoma ( numbers ≥ 3) • Colonoscopicpolypectomy: excision of comfirmedadenomatous polyps (excluding hyperplastic polyps) • Negative endoscopy: no adenomas or CRCs

16. 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)

18. Results • 88,902 participants, follow-up for 22 years • Received endoscopy vs. without endoscopy • Colorectal cancer: 1815 incident cases (2%)

21. Screen colonscopy interval

22. Surveillance colonoscopy interval after removal of adenomatous polyps

26. 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

27. Thanks for your attention!