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Source: Holle LM, Clement JM, Davis LE. Colorectal cancer. In: DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM, eds. Pharmacotherapy: A Pathophysiologic Approach. 10th ed. New York, NY: McGraw-Hill; 2017. Accessed May 20, 2017.


  • Malignant neoplasm involving colon, rectum, and anal canal.


  • Studies suggest development of colorectal cancer related to:

    • Dietary factors.

    • Lifestyle factors.

    • Environmental factors.

    • Inherited susceptibilities.

    • Certain disease states.


  • Multistep process of genetic and phenotypic alterations of normal bowel epithelium structure and function leading to unregulated cell growth, proliferation, and tumor development.

  • Features of colorectal tumorigenesis include:

    • Genomic instability.

    • Activation of oncogene pathways.

    • Mutational inactivation of tumor-suppressor genes.

    • Activation of growth factor pathways.


  • Third leading cause of cancer-related deaths for men and women in United States.

  • Median age at diagnosis is 70 years.

  • Five-year survival rates are about 90% for persons with early stages of colon and rectal cancer.

    • After the tumor has spread regionally to adjacent lymph nodes or tissues, 5-year survival rates drop to about 70% for both colon and rectal cancer.

    • Five-year survival for individuals with metastatic disease is about 13%.


  • Primary prevention aimed at populations at highest risk.

  • Secondary prevention aimed at preventing malignancy in population already manifesting initial disease process.

    • Includes procedures ranging from colonoscopic removal of precancerous polyps detected during screening colonoscopy to total colectomy for high-risk individuals (e.g., familial adenomatous polyposis [FAP]).

  • Chemoprevention.

    • United States Preventive Services Task Force Guidelines.

      • Daily low-dose aspirin for at least 10 years in adults ages 50–59 years who have a life expectancy of at least 10 years and are not at risk for bleeding to prevent both cardiovascular disease and colorectal cancer.

      • Adults ages 60–69 years may also receive low-dose daily aspirin for at least 10 years if the benefits outweigh the risk.

  • Screening techniques.

    • Fecal occult blood testing (FOBT)

    • Flexible sigmoidoscopy: not able to evaluate entire bowel.

    • Total colonic examination.

      • Colonoscopy.

      • Computed tomography colonography.

      • Double-contrast barium enema.

    • United States screening guidelines for average-risk individuals include annual occult fecal blood testing starting at age 50 years and examination of colon every 10 years, depending on procedure.


  • Elevated risk.

    • Physical inactivity and elevated BMI

    • Alcohol intake: stronger association for men than women.

    • Tobacco use.

    • Western diet.

    • Clinical risk factors.

      • Type 2 diabetes, independent of BMI, and physical activity.

      • Metabolic syndrome.

      • Chronic inflammatory diseases.

        • Ulcerative colitis.

        • Crohn’s disease.

    • Genetic susceptibility.

      • Hereditary (10% of cases)

        • FAP

        • Hereditary nonpolyposis colorectal cancer (HNPCC)

        • Lynch syndrome.

      • Familial (30% of cases)

        • First-degree relatives have 2–6 times increased risk as compared to general population.

  • Reduced risk.

    • Risk-to-benefit considerations unresolved:

      • Regular aspirin and NSAID use associated with risk reduction of 30–50%.

      • Exogenous ...

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