Download Adenomatous polyposis coli

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 chainterminating 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 βcatenin 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
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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