Download Relative Risk of Colon Cancer(CRC)

COLON CANCER: Etiology,
Detection, and Prevention
Angel A. Diaz, M.D.
Board Certified Gastroenterologist
Epidemiology
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Colorectal cancer is the 3rd most commonly diagnosed cancer and the
2nd leading cause of cancer death in the United States.
11% of all new cases of cancer are colorectal cancer.
Approximately 148,000 new cases diagnosed each year.
Approximately 58,000 Americans die annually of colon cancer.
Male:female ratio 1:1
Despite the favorable natural history of colorectal cancer and the
availability of a curative surgical procedure, the overall 5 year survival
rate is 62%.
This is mainly because only 35% of new colorectal cancers are
diagnosed at a local stage (I or II).
Epidemiology continued
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35% are diagnosed at a regionally advanced stage (IIor III).
20-25% are diagnosed at a metastatic stage.
Only 10-15% of patients who have symptoms at initial diagnosis have
early stage colorectal cancer.
5 year survival is 90% for localized colorectal cancer, 60% for regional
spread, and 10% for distant metastases.
The average person has a 6% overall lifetime risk of developing
colorectal cancer.
Incidence and mortality have declined over the past two decades.
Risk Factors
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Age: 80% of colorectal cancers occur in patients without risk factors
other than age >50.
The risk of having colon cancer under age 40 is 0.06% compared to
4.19% between ages 60-79.
Family history of colorectal cancer or adenomatous polyps.
Certain hereditary conditions (FAP and HNPCC).
IBD
Diets high in saturated fat and/or low in fiber.
Excess ETOH
Sedentary lifestyle.
Risk Factors continued
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A history colonic adenomas increases one’s risk of developing
subsequent adenomas, especially if the adenoma was large >1cm with
either tubulovillous or villous histology.
Polyps are divided into 3 histologic types: tubular, tubulovillous, and
villous.
The risk that a polyp harbors invasive cancer is related to its size and
histologic type.
Polyps <1cm are associated with ~1% risk of harboring cancer;
between 1-2cm the risk is ~10%; >2cm the risk is ~ 25%.
In general, villous adenomas have 10x the risk of harboring cancer
compared to tubular adenomas of the same size.
Environmental Factors Potentially
Influencing Carcinogenesis in the
Colon and Rectum
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Probably related high fat and low fiber consumption
Possibly related environmental carcinogens and
mutagens
Fecapentaenes (from colonic bacteria)
Heterocyclic amines (from charbroiled and fried meat
and fish)
Beer and ale consumption (especially rectal cancer)
Low dietary selenium
Etiology Of Colon Cancer
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Familial and Environmental factors
HNPCC
Chronic Inflammatory Bowel Disease
FAP and Rare Syndromes
92%
5% - 6%
1%
1%
Molecular Genesis of Sporadic and
Familial Colorectal Cancer
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Sporadic cancers
– Multistep accumulation over many years of acquired
somatic mutations and chromosomal deletions
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Oncogenes: when activated or mutated, give clone of epithelial
cells a growth advantage
Tumor suppressor genes: when inactivated or deleted, fail to
regulate cell cycle, give clone of epithelial cells a growth
advantage
Familial cancers
– Inherited germ-line mutations affect every cell in the
body, cause familial cancer predisposition
Recommendations for Prevention of
Colorectal Cancer
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Primary
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Diet: low in fat, high in fruits, vegetables and fiber
Supplements*: vitamins A, E, C; folate; calcium; selenium
Life habits: activity, normal body weight, avoid smoking
and excessive alcohol
Medications*: Aspirin and other NSAIDs, postmenopausal
hormonal replacement
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*pending positive chemoprevention trials
Recommendations for Prevention of
Colorectal Cancer
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Secondary: resection of colorectal adenomas
Cohort study: proctosigmoidoscopy screening reduced
incidence of rectal cancer by 85% ¤¤
Case-control studies: endoscopy and polypectomy reduced
mortality from distal cancer by 50% to 79% ¥¥
Prospective trial of colonoscopy, polypectomy, and
surveillance: reduced incidence of colorectal cancer by
76% to 90% §§
¤¤ Gilbertsen 1978
¥¥ Newcomb 1992, Selby 1992, Muller 1995
§§ Winawer 1993
Screening Modalities
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FOBT
Flexible sigmoidoscopy
Barium enema
Colonoscopy
CT colonography
Distribution of Colorectal Cancers Within the
Large Intestine. Only Half of Cancers Are Within
Reach of the Flexible Sigmoidoscope.
Rate of Detection of Adenomatous
Polyps and Cancers for Various
Instruments
 Rigid
sigmoidoscope
 35-cm flexible sigmoidoscope
 60-cm flexible sigmoidoscope
 Colonoscope
 Air-contrast barium enema
 Single-column barium enema
30%
40%
55%
95%
90%
85%
Screening and Surveillance of
Relatives of Patients With Sporadic
Colorectal Cancer or Adenomas
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Low familial risk: perform annual FOBT, colonoscopy
every 5 years, beginning at age 40.
– If 1º relative with CRC or an adenoma after age 60
High familial risk: perform colonoscopy every 3-5 years
after age 40
– If 1º relative with CRC at a younger age, or multiple 1º, 2º, or 3º
relatives with CRC
– Sibling with adenoma before age of 60
– Sibling with an adenoma and a parent with CRC
Colorectal Cancer Screening
Recommendations for
Asymptomatic, Average-risk
Population
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Begin screening both men and women at age
50
Annual FOBT, (colonoscopy for positive
screen test)
Colonoscopy every 10 years
Individualize for age and comorbidity
Signs and Symptoms of Colorectal
Cancers
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Initial presentation:
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Late cancers
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Most common with rightsided cases:
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Abdominal pain
Weight loss
Abdominal mass
– Overt or occult rectal
bleeding
– Iron deficiency anemia
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Most common with left
sided cases:
– Change in bowel habits
– Abdominal discomfort
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