Overview

Colorectal cancer is the second leading cause of cancer death in the United States. The disease strikes both men and women, with more than 140,000 cases diagnosed each year. Approximately 50,000 people die from colorectal cancer each year. The good news is that earlier detection of colorectal cancer through screening, coupled with improved treatment, has led to better colorectal cancer survival. Mortality rates have declined by almost three percent per year since 1998.1

The chance of an individual developing cancer depends on both inherited genetic factors as well as environmental or behavioral factors. By understanding what factors can increase the risk of colorectal cancer, you may be able to take steps to reduce your risk or to detect the cancer at an early stage.

Hereditary Factors

People with a family history of colorectal cancer are at increased risk for the disease, but risk is particularly elevated to people with certain inherited genetic conditions. Familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC; also called Lynch Syndrome) each greatly increase the risk of colorectal cancer. FAP and HNPCC account for a relatively small percentage (5-10%) of all colorectal cancers, but people with these conditions have a high lifetime risk of colorectal cancer, and often develop cancer at a much younger age than other people.

HNPCC is the most common type of hereditary colorectal cancer, and results from inherited mutations in genes involved in DNA mismatch repair.2 In individuals with HNPCC, the average age at diagnosis of colorectal cancer is about 45 years. Other cancers that are more common in HNPCC families include cancers of the endometrium (the lining of the uterus), ovary, small intestine, ureter, and renal pelvis.

FAP results from inherited mutations in the adenomatous polyposis coli (APC) gene. People with FAP tend to develop numerous colorectal polyps, and polyps may occur as early as the preteen years.

All people with a family history of colorectal cancer should discuss their history with their physician in order to identify the optimal approach to surveillance and prevention. Screening may need to begin at a very early age for some people.

Other Factors

Inflammatory Bowel Disease (IBD): The two major types of inflammatory bowel disease—ulcerative colitis and Crohn’s disease—substantially increase the risk of colorectal cancer. An estimated 10-15% of deaths among people with IBD are due to colorectal cancer.3 Because of this increased risk, people with IBD often undergo earlier and more frequent colorectal cancer screening.

Diet: Many aspects of diet have been studied in relation to colorectal cancer, often with mixed results. Dietary factors that have been reported to increase the risk of colorectal cancer include red meat and alcohol.4 Research suggests that consideration of an individual’s overall dietary pattern may also be important. A study of more than 76,000 women, for example, found that a diet rich in fruits, vegetables, legumes, fish, poultry and whole grains was linked with a lower risk of colon cancer (but not a lower risk of rectal cancer) than a diet high in red and processed meats, sweets, and refined grains.5

Obesity: Obesity has consistently been linked with an increased risk of colon cancer in men.56 The extent to which obesity influences colon cancer risk in women is less clear, although larger waist circumference has been linked with increased colon cancer risk (but not rectal cancer risk) in both men and women.7

Smoking: Studies of the link between tobacco and risk of colorectal cancer have been inconsistent. A pooled analysis of the Women’s Health Initiative studies found an increased risk of rectal cancer among smokers, but no increased risk of colon cancer.78 Some previous studies, however, have reported a link between smoking and colon cancer.

Prevention

We may not be able to completely eliminate our risk of developing colorectal cancer, but there are steps that we can take to reduce our risk.

Diet: Eating a diet rich in fruits, vegetables, and whole grains may reduce the risk of colorectal cancer in addition to providing other health benefits. Since red meat and alcohol may increase the risk of colorectal cancer, these should be consumed in moderation (if at all). Finally, since obesity may increase the risk of colorectal cancer, it’s important to eat a diet that allows you to achieve or maintain a health body weight.

Exercise: Studies suggest that regular physical activity reduces the risk of colon cancer.9 10 11 Exercise may also reduce the risk of rectal cancer, but results for rectal cancer have been somewhat mixed.

Talk with your doctor before starting an exercise program. If your doctor decides that it’s appropriate for you, you may benefit from following exercise guidelines such as those provided by the American Cancer Society.12 Developed for the general population (and not specifically for cancer survivors), the guidelines recommend that adults engage in at least 30 minutes of moderate-to-vigorous physical activity on five or more days per week. A longer duration of exercise (45 to 60 minutes) may provide additional benefits.

Moderate-intensity activity includes brisk walking and cycling on level terrain. Vigorous activity includes cycling or walking up hills and jogging.

Detection and Treatment of Precancerous Polyps: For cancers such as breast cancer, screening does not prevent the development of the cancer; rather, screening detects the cancer at an early stage when treatment is most likely to be successful. In the case of colorectal cancer, however, screening can sometimes prevent the development of cancer by identifying precancerous polyps. Removing these polyps can prevent the later development of cancer. Colorectal cancer screening tests are described in more detail below.

Nonsteroidal Anti-inflammatory Drugs (NSAIDS): NSAIDS are used to reduce inflammation and pain; they include drugs such as aspirin and ibuprofen. Studies have suggested that NSAIDS reduce the risk of colorectal cancer.13 The potential benefits of regular use of these drugs, however, must be weighed against the potential risks. In 2007, the U.S. Preventive Services Task Force (USPSTF) recommended against routine use of aspirin or other NSAIDS for the prevention of colorectal cancer in individuals at average risk of colorectal cancer.14

The following points contributed to this decision:

  • While higher doses of aspirin appear to reduce the risk of colorectal cancer, lower doses of aspirin do not. Higher doses of aspirin increase the risk of gastrointestinal bleeding, and aspirin has also been linked with an increased risk of hemorrhagic stroke.
  • Similarly, while there is some evidence that non-aspirin NSAIDS may reduce the risk of developing colorectal cancer, these drugs increase the risk of gastrointestinal bleeding and kidney problems. In addition, the class of NSAIDS known as COX-2 inhibitors has been linked with an increased risk of cardiovascular problems.

The USPSTF notes, however “These recommendations do not apply to patients with a personal history of colorectal cancer or other conditions that put them at high risk for the disease.” It is also important to note that these recommendations do not alter previous recommendations about the use of low-dose aspirin in people at increased risk of cardiovascular disease.

Patients at high risk for colorectal cancer as a result of personal or family history may wish to talk with their doctor about steps they can take to reduce their risk. A study of people with hereditary non-polyposis colorectal cancer (HNPCC) found that daily aspirin use cut the risk of colorectal cancer by roughly half.15

Calcium: Calcium may provide a modest colorectal cancer benefit. One study showed that patients taking 1200 mg of calcium daily demonstrated a 20% reduction in colorectal adenoma formation and a 45% reduction in advanced adenoma formation.16 Physicians surmise that a reduction in adenoma formation would lead to a reduction in cancer rates. Furthermore, calcium and Vitamin D may work synergistically to decrease adenoma formation.17

Vitamin D: Vitamin D is a fat-soluble vitamin that comes from dietary supplements, foods such as fortified milk and cereal, certain kinds of fish (including salmon, mackerel, and tuna), and exposure to sunlight. Vitamin D is hypothesized to play a role in the prevention of some types of cancer, including colon cancer. According to results from two large studies – the Health Professionals Follow-up Study and the Nurses’ Health Study – individuals with higher blood levels of vitamin D may have a reduced risk of developing colon cancer.18

Preventive surgery: Preventive surgery may be recommended for some people at very high risk of colorectal cancer, such as those with FAP. Surgery is performed to remove the colon (and sometimes the rectum and other organs as well) before cancer develops.

Screening and Early Diagnosis

For many types of cancer, progress in cancer screening has offered promise for earlier detection and higher cure rates. The term screening refers to the regular use of certain examinations or tests in persons who do not have symptoms of cancer.

Screening is crucial for the prevention and early detection of colorectal cancer. The American Cancer Society currently recommends that people at average risk of colorectal cancer begin being screened for colorectal cancer at the age of 50.  Screening may need to begin at a much earlier age for people with a personal or family history of adenomatous polyps, FAP, HNPCC, colorectal cancer, or chronic inflammatory bowel disease.

Several screening strategies are currently available. These include the fecal occult blood test (FOBT), flexible sigmoidoscopy, colonoscopy and double contrast barium enema. The frequency of screening depends on the method. In general, FOBT is performed every year, sigmoidoscopy is performed every five years, and colonoscopy is performed every 10 years. Individuals interested in colorectal cancer screening should discuss the options with their physician in order to determine the most appropriate procedure.

According to recommendations from the U.S. Preventive Services Task Force (USPSTF), routine colorectal cancer screening should continue until the age of 75.19 Patients over this age may wish to talk with their physician about the need for continued screening.

Fecal Occult-Blood Test (FOBT): The fecal occult-blood test checks for hidden blood in the stool. Recently, results from an 18-year study indicated that annual or biannual FOBT could significantly reduce the incidence of colorectal cancer. If positive, this test indicates the presence of bleeding polyps and the need for further screening, such as colonoscopy. The further screening tests allow the identification and removal of polyps, which results in a reduced incidence of colorectal cancer.

Fecal Immunochemical Test (FIT): Fecal immunochemical tests are a newer type of fecal occult-blood test. Unlike traditional FOBT, FIT does not require drug or dietary restrictions on the part of the patient.

Flexible sigmoidoscopy: During this procedure, a physician uses a lighted tube to look inside the rectum and the lower part of the colon (sigmoid colon) for polyps or areas suspicious for cancer. The physician may perform a biopsy in order to collect samples of suspicious tissues or cells for closer examination. This is an outpatient procedure that does not require sedative anesthesia or pain medication. There are no or few complications associated with this procedure.

Colonoscopy: During this procedure, a longer flexible tube that is attached to a camera is inserted through the rectum, allowing physicians to examine the internal lining of the colon and rectum for polyps or other abnormalities. The physician may perform a biopsy in order to collect samples of suspicious tissues or cells for closer examination. This is a more difficult procedure than sigmoidoscopy to perform, requiring anesthesia or heavy sedation, but it allows the entire colon (sigmoid colon, descending colon, transverse colon, and ascending colon) and rectum to be viewed. Significant complications occur in 0.1-0.3% of patients or less.1920

Double-contrast barium enema: A chalky substance called barium is inserted through the rectum and into the colon and rectum. The patient then undergoes x-rays of the colon and rectum so that the physician can evaluate the area for polyps or other abnormalities. The barium helps open the colon so that the x-rays are more detailed and clear.

While these screening strategies help to monitor for the development of adenomatous polyps and colorectal cancer, other tests exist which may allow physicians to identify patients who are at risk for the development of colorectal cancer.

Predictive genetic testing: If your history suggests that your family has HNPCC or FAP, your doctor may discuss genetic testing with you. If you undergo genetic testing and are found to carry one of the HNPCC or FAP gene mutations, there are steps that you can take to manage your cancer risk.

Strategies to Improve Screening and Early Detection of Colon Cancer

The potential for earlier detection and higher cure rates increases with the advent of more refined screening techniques. In an effort to provide more screening options and perhaps more effective prevention strategies, researchers continue to explore new techniques for the screening and early detection of cancer.

Several new strategies for the screening of colorectal cancer have recently emerged. Despite progress in this area, it is still important that individuals continue to utilize the standard screening procedures in an effort to maintain health and detect colorectal cancer early when it is most treatable. However, these new procedures hold promise for earlier and more reliable detection of colorectal cancer and some individuals may be interested in participating in clinical trials that will help to determine the effectiveness of these new techniques.

DNA stool test: This newer screening procedure involves looking for abnormal DNA in stool samples. Changes in DNA occur as tumors develop in the colon. The tumors shed cells into the intestine, which makes it possible to detect the abnormal DNA cells in stool samples. This simple, non-invasive screening procedure has proven effective in some clinical studies21 but is expensive to perform. Research is ongoing to determine the feasibility of using this as a standard screening procedure.

Virtual colonoscopy: In virtual colonoscopy (also called CT colonography), spiral CT scanners scan the entire colon to produce a 3-D image. The procedure allows for the complete visualization of the colon more quickly and less invasively than with conventional colonoscopy, although patients who have polyps detected will still need to undergo conventional colonoscopy to have the polyps removed. Virtual colonoscopy is a promising new technique, but more research may be needed before it becomes a standard screening procedure for colorectal cancer.

References


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15 Burn J, Gerdes A-M, Macrae F et al. Long-term effect of aspirin on cancer risk in carriers of hereditary colorectal cancer: an analysis from the CAPP2 randomised controlled trial. Lancet. Early online publication October 28, 2011

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21 Itzkowitz SH, Brand R, Jandorf L, et al.  A simplified, noninvasive stool DNA test for colorectal cancer detection. American Journal of Gastroenterology. 2008; 103:2862-70.

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