Colon Cancer

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  • Colon and rectal cancers (CRC) are often grouped together but are two distinct clinical entities that differ in their prognosis, presentation, staging, and management.
  • CRC is the second leading cause of cancer deaths and is the third most common cancer in men and women in the United States.
  • Screening for colon cancer reduces the incidence of and mortality from colon cancer.


  • 93,090 new cases of colon cancer in 2015
  • 49,700 deaths from CRC combined were estimated in the United States in 2015 (1).
  • Incidence is equal between men and women.

  • The lifetime risk for developing colon cancer in the United States is about 1 in 21 (4.8%).
  • Incidence and death rates have been declining due to improved screening, prevention, and treatment.

Etiology and Pathophysiology

  • Progression from the first abnormal cells to the appearance of colon cancer usually occurs over 10 to 15 years, a disease characteristic that contributes to the effectiveness of prevention.
  • High-risk polyp findings include multiple polyps, villous polyps, and larger polyps.
  • Hyperplastic polyps are less likely to evolve into CRC.
  • Multiple genetic and environmental factors have been linked to the development of CRC.

  • <10% of CRC cases are linked to an inherited gene.
    • APC, a tumor suppressor gene, is altered in familial adenomatous polyposis (FAP).
    • Genes encoding DNA mismatch repair (MMR) enzymes are implicated in hereditary nonpolyposis colon cancer (HNPCC): MLH1, MSH2, MSH6, PMS1, PMS2, and others.
    • STK11, a tumor suppressor gene, is altered in Peutz-Jeghers syndrome.
  • Sporadic cases of CRC have been linked to oncogenes: Kras, c-Myc, c-Src, HER-2/neu, and others.

Risk Factors

  • Age: >90% of people diagnosed with colon cancer are >50 years of age.
  • Personal history of colorectal polyps
    • Risk increases with multiple polyps, villous polyps, larger polyps, and presence of dysplasia.
  • Personal history of cancer
    • 30% increase in risk of developing metachronous (new primary tumors unrelated to the patients’ previous cancers) colon cancer
    • 2–4% incidence of local recurrence with colon cancer, 3–5% incidence of synchronous colon cancer
  • History of inflammatory bowel disease (IBD)
    • Prevalence of CRC in ulcerative colitis and Crohn disease is ~3%, with a cumulative risk of CRC of 2% at 10 years, 8% at 20 years, and 18% at 30 years.
  • Family history of CRC
    • Having a single first-degree relative with a history of CRC increases risk 1.7-fold.
    • Risk is more than double for those who have a history of CRC or polyps in:
      • Any first-degree relative <60 years of age
      • ≥2 first-degree relatives, regardless of age
  • Inherited syndromes
    • HNPCC (formerly Lynch syndrome)
      • Often develops at young age (Average age at diagnosis of CRC is 44 years.)
      • Lifetime risk of CRC is 52–69%.
      • Accounts for ~2% of all CRCs
    • FAP
      • Affected individuals develop hundreds to thousands of polyps in colon and rectum.
      • CRC usually present by age 40 years
      • Accounts for <1% of CRCs
    • Peutz-Jeghers syndrome
      • Individuals may have hyperpigmented mucocutaneous lesions (mouth, hands, feet) and large polyps in GI tract.
      • 81–93% risk for CRC and increased risk for other cancers
  • Race and ethnicity
    • African Americans have the highest CRC incidence and mortality rates in the United States. It is unclear whether this is biologic or due to lower rates of access to screening.
    • Colonoscopy is underutilized, particularly in minorities.
    • Several different gene mutations have been identified among Ashkenazi Jews.
  • Lifestyle factors that increase risk
    • Smoking, obesity, diet high in fat and low in fiber

General Prevention

  • Optimal screening method for colon cancer is unclear. Stool-based testing such as guaiac fecal occult blood test (gFOBT) and fecal immunochemical test (FIT) or FIT-DNA tests are less invasive, but endoscopic testing such as flexible sigmoidoscopy or colonoscopy offers ability to provide intervention if polyp discovered.
  • Lifestyle factors that may reduce risk:
    • Low-fat, high-fiber diet (rich in fruits and vegetables)
    • Supplementation with vitamin D, calcium, folate, and fiber may lower CRC risk; more research is needed to understand how diet affects risks of CRC.

    The U.S. Preventive Services Task Force (USPSTF) strongly recommends screening adults, beginning at age 50 years and continuing until age 75 years and gives this an “A” grade, meaning screening’s benefits far outweigh its harms.

  • Screening methods include
    • Colonoscopy every 10 years
    • Flexible sigmoidoscopy every 5 to 10 years (2)[C]
    • FIT annually (1)[C]
    • Fecal occult blood testing annually (1)[A]
    • Stool DNA (sDNA) test every 3 years (2)[C]
    • Note: The USPSTF does not recommend barium enema as a screening test and concludes the evidence is insufficient to assess the benefits and harms of CT colonography and sDNA testing as screening modalities for CRC. The USPSTF also recommends AGAINST routine screening for CRC in adults 76 to 85 years of age but acknowledges there may be considerations that support screening in certain patients and recommends AGAINST screening those age >85 years.
  • American Cancer Society recommends screening with colonoscopy every 10 years. For those patients refusing colonoscopy, an alternative cancer detection tests method is recommended.
  • Screening in high-risk groups:
    • The American College of Gastroenterology recommends screening African American patients starting at age 45 years.
    • People with a history of polyps need frequent colonoscopy screening, depending on risk.
    • People who have a first-degree relative or two second-degree relatives with CRC or adenomatous polyps before age 60 years should begin colonoscopy at age 40 or 10 years younger than the age of relative at cancer diagnosis, whichever is earlier.
    • People with IBD should have regular surveillance colonoscopy with biopsies to detect dysplasia; guidelines generally indicate starting surveillance by 8 to 10 years of onset of symptoms followed by surveillance every 1 to 2 years.
    • Genetic testing may be appropriate for individuals with a strong family history of CRC or polyps:
      • Family members of a person affected by HNPCC should start colonoscopy surveillance at age 25 years.
      • Individuals with suspected FAP should have yearly flexible sigmoidoscopy beginning at age 10 to 12 years; those who test positive for the gene linked to FAP may consider colectomy.

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