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

• Polyp-Cancer sequency ?

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

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

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.

• 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 development

Kathleen H. Biology Of The APC Tumor Suppressor. J Clin Oncol 2000;18:1967-1979.

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.

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

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

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

• 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

• 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

• 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)

Results

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

Screen colonscopy interval

Surveillance colonoscopy interval after removal of adenomatous polyps

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

Thanks for your attention!