• 3rd leading cause of cancer deaths (male and female)
  • Most commonly located in rectum and sigmoid colon
  • Risk factors
    • family history
    • IBD
      • ulcerative colitis has greater risk than Crohn's
    • colorectal polyps
    • diet low in fiber
    • Streptococcus bovis bacteremia
    • tobacco use
    • large villous adenomas
    • polyp syndromes
      • e.g., Familial adenomatous polyposis (FAP)
  • Decreased risk associated with
    • NSAID use
    • estrogen
    • statins
  • Pathogenesis
    • 2 molecular pathways that lead to CRC
      • microsatellite instability pathway 
        • loss-of-function mutations in DNA mismatch repair genes
          • leads to sporadic and HNPCC syndrome (see below)
      • APC/β-catenin (chromosomal instability) pathway
        • leads to FAP 
    • Follows the adenoma-carcinoma sequence - begins with APC mutation, with a step-wise accumulation of genetic mutations, ultimately concluding with p53 inactivation as the deciding factor in the progression from adenomatous polyp to carcinoma 
  • Symptoms
    • Right sided lesions
      • more likely to bleed, less likely to obstruct
        • due to wider lumen
      • fecal occult blood
        • leading to iron deficiency
      • postprandial discomfort
    • Left sided lesions
      • more likely to obstruct, less likely to bleed
        • due to narrower lumen
      • change in bowel habits
      • pencil thin stools
      • abdominal mass
      • Strep. bovis endocarditis
    • systemic symptoms (malaise, fatigue, weight loss)
  • Physical exam
    • palpable mass on rectal exam (if large enough)
  • Barium enema X-ray
    • "apple core" lesion 
  • Colonoscopy
    • gold standard
  • Labs
    • microcytic anemia
      • iron deficiency anemia in an elderly male is colon cancer until proven otherwise
    • fecal occult blood test
      • lacks sensitivity and specificity as it only tests for globin with a peroxidase
        • false positive with high meat diet (myoglobin), radishes (peroxidase)
  • Hereditary Nonpolyposis Colorectal Cancer (HNPCC) / Lynch syndrome
    • single polyp can turn to cancer
    • due to loss-of-function in DNA mismatch repair genes (MLH1, MSH2/6, PMS3)
    • Lynch Syndrome I (HNPCC I)
      • AD inheritance
      • predisposition to right sided CRC 
    • Lynch Syndrome II (HNPCC II)
      • same features of Lynch I
      • plus extra-colonic cancers, especially
        • carcinoma of ovary, endometrium, small bowel, stomach, pancreas
        • transitional cell CA
  • Surgical
    • resection
  • Medical
    • chemotherapy
Prognosis, Prevention, and Complications
  • Screening
    • screen patients > 50 years of age with stool occult blood test and colonoscopy
    • begin at age 40 with patients who have family history of CRC
    • annual digital exam
  • Recurrence monitoring
    • use CEA tumor marker 
      • not used for diagnosis

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