Description

• Colorectal cancer (CRC) denotes a neoplasm that develops in the colon or rectum.
• CRC is the 2nd leading cause of cancer deaths and is the 3rd most common cancer in men and women in the US.
• Screening for CRC reduces the incidence of, and mortality from, CRC.

Epidemiology

Incidence
In the US in 2008, 142,950 new cases of CRC were diagnosed, and 52,857 people died from CRC.

• Overall lifetime risk for developing CRC in the US is about 1/19 (5.4%).
• Death rates have been declining due to improved screening, prevention, and treatment.

Risk Factors

• Age: >90% of people diagnosed with CRC are >50 years of age.
• Personal history of colorectal polyps:
  • Risks increase with multiple polyps, villous polyps, and larger polyps.
• Personal history of cancer:
  • Rectal cancer has a higher incidence of local recurrence than proximal cancers (20–30% vs. 2–4%).
• History of inflammatory bowel disease:
  • 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 (1,2).
• Family history of CRC (although most CRCs occur in people without a family history):
  • Risk doubles in those who have a single 1st-degree relative with a history of CRC.
  • Risk is >double for those who have a history of CRC or polyps in:
    • Any 1st-degree relative <60 years of age
    • ≥2 1st-degree relatives, regardless of age
• Inherited syndromes:
  • Familial adenomatous polyposis (FAP):
    • Affected individuals develop hundreds to thousands of polyps in colon and rectum.
    • CRC usually present by age 40
    • Accounts for about 1% of CRCs
  • Hereditary nonpolyposis colon cancer (HNPCC, also called Lynch syndrome):
    • Often develops at a relatively young age
    • Lifetime risk of CRC 70–80%
    • Accounts for ~3–4% of all CRCs
  • Peutz-Jeghers syndrome:
    • Individuals may have freckles (mouth, hands, feet) and large polyps in GI tract.
    • Greatly increased risk for CRC and cancers
• Race and ethnicity:
  • African Americans have highest CRC incidence and mortality rates in the US.
  • Several different gene mutations have been identified among Ashkenazi Jews.
• Miscellaneous:
  • Streptococcus bovis bacteremia is associated with CRC.
  • Patients with acromegaly are at increased risk.

• Most result from acquired DNA mutation.
• There does not seem to be a single genetic pathway to CRC, although mutations are frequently seen in APC, K-Ras, p53, and SMAD4.
• A small percentage of colon cancers are known to be caused by inherited gene mutations:
  • APC, a tumor suppressor gene, is altered in FAP.
  • Genes encoding DNA repair enzymes implicated in HNPCC: MLH1, MSH2, MSH6, PMS1, PMS2, and others
  • STK11, a tumor suppressor gene, is altered in Peutz-Jeghers syndrome.

General Prevention

• Diets high in fruits and vegetables have been linked with decreased risk; those high in red and processed meats may increase CRC risk.
• People who are physically inactive are at higher risk for CRC.
• Long-term smokers are more likely than nonsmokers to develop and die from CRC.
• CRC has been linked to heavy alcohol consumption; may be related to low folic acid.
• Some studies suggest that vitamin D, calcium, and folate may lower CRC risk.
• NSAIDs may reduce risk in some groups; however, experts do not recommend NSAID use as a cancer prevention strategy in people at average risk for CRC.
• Colon cancer screening is one of the most powerful tools in preventing colon cancer.

ALERT
The United States Preventive Services Task Force (USPSTF) strongly recommends that clinicians screen men and women between the ages of 50 and 75 for CRC using one of the following: Fecal occult blood testing, sigmoidoscopy, or colonoscopy (3)[A].

• Less evidence-based American Cancer Society recommendations include completing one of the following tests (1)[C]:
  • Fecal occult blood testing (FOBT) annually
  • Fecal immunochemical test (FIT) annually
  • Stool DNA test (sDNA) (not available in the US)
  • Flexible sigmoidoscopy every 5 years
  • Double-contrast barium enema every 5 years
  • Colonoscopy every 10 years
  • CT colonography every 5 years (colonoscopy completed if positive)
  • 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 stool DNA testing as screening modalities for CRC (2)[A].
  • Digital rectal exam (DRE), alone or in combination with a 1-sample FOBT or FIT test, is not an acceptable method for CRC screening.
• Screening in high-risk groups (3):
  • People with a personal history of polyps need more frequent colonoscopy screening, depending on risk (i.e., 1 or 2 <1 cm polyps with low-grade dysplasia is deemed low risk and may warrant repeat colonoscopy in 5–10 years; decision is influenced by family history, age, quality of initial colonoscopy, and patient comorbidities).
  • People who have a family history of CRC should begin colonoscopy at age 40 or 10 years younger than the age of relative at cancer diagnosis, whichever is earlier.
  • People with a family history of polyps should begin colonoscopy screening at age 40.
  • People with inflammatory bowel disease (IBD) should have regular surveillance colonoscopy with biopsies to detect dysplasia; guidelines for timing and location vary by professional society, but generally indicate starting surveillance by ~8 years of onset of disease followed by surveillance every 1–2 years.
  • Genetic testing may be appropriate for individuals with a strong family history of CRC or polyps:
    • Family members of a person affected by HNPCCC should start colonoscopy screening as early as age 20.
    • Individuals who test positive for the gene linked to FAP should start colonoscopy screening in their teens.

Pathophysiology

• Progression from the first abnormal cells to the appearance of CRC usually occurs over 10–15 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 colorectal cancer.

Etiology

Multiple genetic and environmental factors have been linked to the development of CRC.