II. Risk Factors: Colorectal Cancer

  1. Age >50 years (accounts for 90% of Colon Cancer)
  2. Inflammatory Bowel Disease
    1. Ulcerative Colitis
      1. Risk increases with duration since diagnosis (2% at 10 years of disease, 18% at 30 years of disease)
    2. Crohns Disease
      1. Lifetime risk of Colorectal Cancer: 4-5%
  3. Past Medical History
    1. Adenomatous polyps >5mm (Confers RR of 2-3 times)
    2. Hamartomatous Polyposis syndromes
    3. Cholecystectomy
    4. Pelvic irradiation
  4. Family History (non-syndrome related)
    1. Higher risk Family History Criteria (RR 3-4x)
      1. One first degree relative with Colorectal Cancer or advanced adenoma before age 60 years
      2. Two first degree relatives with Colorectal Cancer or advanced adenoma at any age
    2. Moderate risk Family History Criteria (RR 2-3x)
      1. One first degree relative with Colorectal Cancer or advanced adenoma age 60 years or older
      2. Two second degree relatives with Colorectal Cancer or advanced adenoma at any age
  5. Hereditary Syndromes
    1. Attenuated Familial Adenomatous Polyposis (10-99 synchronous advanced adenomas)
      1. Diagnosed on average by age 58 years, and 69% develop Colon Cancer by age 80 years old
    2. Familial Adenomatous Polyposis (>100 synchronous advanced adenomas)
      1. Diagnosed on average by age 39 years, and 87% develop Colon Cancer by age 45 years old
    3. Hereditary non-polyposis Colon Cancer (Lynch Syndrome)
      1. Diagnosed on average by age 45 years, and 75-80% lifetime Colon Cancer risk
      2. Autosomal Dominant condition
      3. Most common cause of inherited Colorectal Cancer
    4. MUTYH-Associated Polyposis (<100 Colorectal Adenomas)
      1. Autosomal Recessive risk for Colorectal Cancer
      2. Colorectal Cancer risk 19% by age 50, and 43% by age 60 years
    5. Peutz-Jeghers Syndrome (Hamartomatous Polyposis)
      1. Symptomatic polyps by age 10 to 30 years
    6. Sessile Serrated Adenomatous Polyposis
      1. Diagnosed on average by age 62 years, and 25-70% have Colon Cancer at time of diagnosis
  6. Lifestyle related risks
    1. Tobacco abuse
      1. Current smokers have a 2 fold higher Relative Risk of high-risk adenomas or Colorectal Cancer
      2. Botteri (2008) Gastroenterology 134(2):388-95 [PubMed]
    2. Obesity
      1. BMI 35-40 associated with Colorectal Cancer mortality Relative Risk 1.8 in men, 1.4 in women
        1. Calle (2003) N Engl J Med 348(17): 1625-38 [PubMed]
      2. Bariatric Surgery reduced Colorectal Cancer rtisk by 27%
        1. Afshar (2014) Obes Surg 24(10): 1793-99 [PubMed]
  7. Dietary Risk Factors
    1. Coffee does not have a consistent impact on Colorectal Cancer risk
    2. Dairy products have a minimal impact on Colorectal Cancer risk
    3. High Dietary Fat
      1. Saturated and polyunsaturated fat increases adenomatous polyp development
      2. High fat diet is not associated with Colorectal Cancer development
        1. Howe (1997) Cancer Causes Control 8:215-28 [PubMed]
      3. Low Fat Diet does not appear to lower Colorectal Cancer risk
        1. Prentice (2007) J Natl Cancer Inst 99(20): 1534-3 [PubMed]
    4. Red Meat
      1. Foods with possible higher risk: Salt-cured, pickled, smoked, barbeque
      2. Red meat consumption does increase Colorectal Cancer risk
        1. Chan (2011) PLoS One 6(6): e20456 [PubMed]

III. Prevention: Colorectal Cancer

  1. High Physical Activity
    1. Mahmood (2017) Int J Epidemiol 46(6): 1797-13 [PubMed]
  2. High fruit and vegetable intake
  3. High Dietary Fiber intake
    1. Previously recommended for longterm prevention
      1. However no data to support fiber in prevention of adenomas or Colorectal Cancer
    2. Does not prevent Colorectal Cancer or adenomatous polyps
      1. Schatzkin (2000) N Engl J Med 342:1149-55 [PubMed]
      2. Yao (2017) Cochrane Database Syst Rev (1):CD003430 [PubMed]
    3. Sources
      1. Whole grain cereals
      2. Legumes
      3. Fruits and vegetables
      4. Water insoluble (wheat bran) fiber may be best
  4. High Dietary Calcium intake (1200 mg qd)
    1. Prevents adenoma recurrence
      1. Baron (1999) N Engl J Med 340:101-7 [PubMed]
    2. Decreases risk of histologically advanced polyps
      1. Wallace (2004) J Natl Cancer Inst 96:921-5 [PubMed]
  5. Medications: None are recommended for routine prevention (unless indicated for other reason)
    1. General
      1. Aspirin, NSAIDs, COX-2 Inhibitors not recommended
      2. Despite effectiveness in prevention, risks are high
      3. (2007) Am Fam Physician 76:109-113 [PubMed]
    2. Aspirin
      1. More effective in reduction of proximal Colorectal Cancers
      2. Reduces adenoma Incidence in high risk patients
        1. Greatest risk reduction at >14 tablets per week
        2. Chan (2004) Ann Intern Med 140:157-66 [PubMed]
      3. However, increased risk of Gastrointestinal Bleeding and Hemorrhagic CVA
        1. Not recommended for CRC prevention in average-risk patients
        2. Consider in those with other indications (esp. 10 year cardiovascular risk >10%)
    3. NSAIDs
      1. Adverse effects (e.g. Gastrointestinal Bleeding, nephrotoxicity) limit chronic preventive use
      2. Sulindac prevented neoplasia in familial polyposis
        1. Janne (2000) N Engl J Med 342:1960-8 [PubMed]
    4. COX-2 Inhibitors
      1. Celecoxib prevented neoplasia in familial polyposis
      2. Steinbach (2000) N Engl J Med 342:1946-52 [PubMed]
    5. Postmenopausal Hormone Replacement
      1. Studies demonstrate lower overall Colon Cancer risk
      2. However, those diagnosed with Colon Cancer were at a more advanced stage
      3. Chlebowski (2004) N Engl J Med 350:991-1004 [PubMed]
    6. Antioxidants
      1. No benefit with Beta Carotene, Vitamin A, Vitamin C, Vitamin E, Selenium
      2. Increased adenomatous polyp risk with Vitamin E
      3. Bjelakovic (2006) Aliment Pharmacol Ther 24:281-91 [PubMed]
    7. High Folate or methionine intake
      1. No significant benefit in Colorectal Cancer Prevention
      2. Cole (2007) JAMA 297(21): 2351-9 [PubMed]
    8. Vitamin D
      1. No consistent benefit in Colorectal Cancer Prevention
      2. Chung (2011) Ann Intern Med 155(12): 827-38 [PubMed]
    9. Statins
      1. Observational studies demonstrate a 30% reduction in Colon Cancers
      2. Randomized controlled studies needed before a recommendation can be made
      3. Poynter (2005) N Engl J Med 352: 2184-2192 [PubMed]

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